ONCOLOGY LETTERS 15: , 2018

Transcription

1 ONCOLOGY LETTERS 15: , 2018 Effects of dexmedetomidine on inflmmtory fctors, T lymphocyte subsets nd expression of NF κb in peripherl blood mononucler cells in ptients receiving rdicl surgery of colon crcinom KUN WANG nd CHENGWEN LI Deprtment of Anesthesiology, Jining No. 1 People's Hospitl, Jining, Shndong , P.R. Chin Received December 14, 2017; Accepted Februry 16, 2018 DOI: /ol Abstrct. The effects of dexmedetomidine on inflmmtory fctors, T lymphocyte subsets nd expression of nucler fctor-κb (NF-κB) in peripherl blood mononucler cells in ptients receiving rdicl surgery of colon crcinom were investigted. A totl of 141 ptients receiving rdicl surgery of colon crcinom from Jnury 2014 to April 2017 were divided into two groups rndomly. The ptients in the tretment group were given dexmedetomidine, while the ptients in the control group were treted with sline. Results showed tht there were no significnt differences in preopertive levels of NF-κB, sicam-1 nd IL-8 between the two groups. However, the bove three indexes of the groups were ll significntly incresed t 0.5 nd 24 h fter opertion, nd the results showed tht the control group hd higher degree of increse (P<0.05). It ws lso found tht the chnges in levels of IL-6 nd CRP in ptients were the sme s those of the bove three indexes; in other words, the degree of the increse in the control group ws significntly higher thn tht in the tretment group fter opertion. Moreover, it ws found tht there ws little difference in the preopertive Rmsy score of ptients between the two groups. The scores t 0.5 nd 12 h fter opertion in the tretment group were significntly higher thn those in the control group (P<0.05). It ws lso found tht the intropertive nd postopertive dosges of fentnyl in the tretment group were significntly less thn those in the control group (P<0.05). We cn conclude tht the ppliction of dexmedetomidine during nesthesi in ptients receiving rdicl opertion of colon crcinom hs better clinicl tretment effect, which cn reduce the secretion of inflmmtory Correspondence to: Dr Chengwen Li, Deprtment of Anesthesiology, Jining No. 1 People's Hospitl, 6 Jinkng Rod, Jining, Shndong , P.R. Chin E-mil: lichwen2008@126.com Key words: dexmedetomidine, colon crcinom, inflmmtory fctors, T lymphocyte subsets, peripherl blood mononucler cells fctors, decrese the inhibition of immunity nd reduce the use of fentnyl. Introduction Ptients receiving rdicl opertion of colon crcinom need nesthesi during the surgicl tretment (1,2). At present, dexmedetomidine, s new type of drenergic receptor gonist, is incresingly widely used in the field of nesthesi (3-5). The drug hs been commonly used s the preopertive sedtive, regionl nesthesi djuvnt nd generl nesthesi djuvnt (6,7). It is cliniclly found tht the drug lso hs n nti-inflmmtory effect (8-10). Therefore, 141 ptients receiving rdicl opertion of colon crcinom in Jining No. 1 People's Hospitl (Jining, Chin) from Jnury 2014 to April 2017 were selected in this study, nd dexmedetomidine nesthesi ws induced, so s to explore the nti-inflmmtory nd immune effects of the sedtive, nd provide more scientific clinicl bsis. Ptients nd methods Generl dt. A totl of 141 ptients receiving rdicl opertion of colon crcinom in Jining No. 1 People's Hospitl (Shndong, Chin) from Jnury 2014 to April 2017 were collected, including 69 cses in the control group nd 72 cses in the tretment group. There were 33 mles nd 36 femles in the control group, nd 36 mles nd 36 femles in the tretment group. In the control group, they were ged yers with n verge ge of 45.3±5.0 yers, nd in the tretment group, they were ged yers with n verge ge of 42.5±4.3 yers. Ptients in the two groups were ll in I-II of Americn Society of Anesthesiologists (ASA) grde. This study ws pproved by the Ethics Committee of Jining No. 1 People's Hospitl. Signed written informed consents were obtined from ll ptients or their gurdins before the study. Exclusion criteri: Ptients with dmge in hert, liver or kidney, or systemic immune system diseses. Methods. Before the opertion, the ptients were fsting for 12 h before nesthesi nd generl nesthesi ws performed before the opertion. The method of nesthesi induction is

2 7154 WANG nd LI: EFFECTS OF DEXMEDETOMIDINE ON PATIENTS WITH COLON CARCINOMA Tble I. Comprison of generl dt between two groups (men ± SD). Age Body weight ASA Anesthesi time Opertion time Amount of bleeding Group (yers) (kg) grde (min) (min) (ml) Tretment group 42.5±4.3 52±3.5 I-II 109.2± ± ±3.2 Control group 45.3±5.0 56±4.3 I-II 110.5± ± ±3.0 Tble II. Effects of NF-κB in peripherl blood mononucler cells nd serum sicam-1 nd IL-8 levels in two groups (men ± SD). Group Time NF-κB (U/l) sicam-1 (mg/l) IL-8 (pg/ml) Tretment group Preopertive 24.56± ± ± h fter opertion 33.79± ± ± h fter opertion 28.31± ± ±1.9 Control group Preopertive 25.06± ± ± h fter opertion 42.59±3.65,b 588.5±8.6,b 59.8±3.0,b 24 h fter opertion 32.32±2.86,b 543.1±9.5,b 34.3±2.8,b Compred with tht before opertion, P<0.05; b compred with tht in tretment group, P<0.05. s follows: The ptients were given intrvenous injection of midzolm (0.05 mg/kg), vecuronium (0.1 mg/kg), etomidte (0.3 mg/kg) nd fentnyl (1.0 µg/kg). During ventiltion, end-tidl prtil pressure of crbon dioxide (PETCO2) ws set t mmhg nd fentnyl ws dministered vi veno-micropump trget control with the infusion rte of µg/(kg min). The tidl volume of the ventiltor ws set t 8-10 ml/kg, with frequency of times/min, nd PETCO2 of mmhg. The infusion rte of fentnyl ws controlled to djust the depth of nesthesi. Intrvenous injection of urpidil or ephedrine ws selected ccording to the chnge in SBP vlue. Sevoflurne inhltion ws discontinued following the completion of opertion nd fentnyl (0.5 µg/kg) ws dministered intrvenously fter opertion for systemic nlgesi. The ptients in the tretment group were given pump infusion of dexmedetomidine [1 µg/kg over min s loding dose; then the pump flow rte ws set s 1 µg/ (kg h)] before opertion, while the ptients in the control group received pump injection of the sme mount of norml sline. Evlution of the efficcy. Rmsy sedtion score: Ptients were scored before opertion nd t 0.5, 12 nd 24 h fter opertion, respectively. Ptients with irritbility nd restlessness: 1 point; ptients who were coopertive nd quiet: 2 points; ptients with lethrgy nd obeying orders: 3 points, ptients who could be wkened during sleep: 4 points; ptients with slow rection when being clled: 5 points; ptients who could not be wkened when being clled: 6 points. Observtionl indexes. The levels of nucler fctor-κb (NF-κB) in peripherl blood mononucler cells, serum soluble intercellulr dhesion molecule-1 (sicam-1), interleukin-8 (IL-8), serum IL-6, tumor necrosis fctor-α (TNF-α) nd C-rective protein (CRP) of ptients in the two groups were observed during periopertive period. Besides, the levels of T lymphocyte subsets of ptients in two groups were observed by flow cytometry. The dosges of fentnyl used during opertion nd fter opertion were recorded. Sttisticl nlysis. Dt were processed by SPSS 17.0 softwre (SPSS, Inc., Chicgo, IL, USA). Mesurement dt nd counting dt were expressed by men ± stndrd devition (SD) nd n, respectively, nd t-test nd chi-squre test were used for intergroup comprison. P<0.05 suggested tht the difference ws sttisticlly significnt. Results Comprison of generl dt between two groups. The generl dt of ptients in the two groups were compred: In the tretment group, the verge ge ws 42.5±4.3 yers, body weight ws 52±3.5 kg, ASA grde ws I-II, nesthesi time 109.2±7.4 min, opertion time 98.7±4.3 min, nd mount of bleeding ws 59.2±3.2 ml; in the control group, the verge ge ws 45.3±5.0 yers, body weight 56±4.3 kg, ASA grde I-II, nesthesi time 110.5±7.4 min, opertion time 99.3±4.8 min, nd mount of bleeding ws 58.8±3.0 ml. The nesthesi time nd the mount of bleeding in the two groups were similr (Tble I). Effects of NF-κB in peripherl blood mononucler cells nd serum sicam-1 nd IL-8 levels in the two groups. There were no significnt differences in the preopertive levels of NF-κB, sicam-1 nd IL-8 in ptients between the two groups. However, they were incresed nd then decresed t 0.5 nd 24 h fter opertion; the contents of three indexes of ptients in both groups were significntly incresed t two time-points fter opertion, nd the degree of the increse in control group

3 ONCOLOGY LETTERS 15: , Tble III. Comprison of serum levels of IL-6, TNF-α nd CRP in ptients between two groups (men ± SD). Group Time IL-6 (pg/ml) TNF-α (pg/ml) CRP (mg/l) Tretment group Preopertive 3.25± ± ± h fter opertion 70.56± ± ± h fter opertion 60.72± ± ±0.12 Control group Preopertive 3.69± ± ± h fter opertion 90.56±3.65,b 16.75± ±0.21,b 24 h fter opertion 67.97±3.98,b 18.98± ±0.32 Compred with tht before opertion, P<0.05; b compred with tht in tretment group, P<0.05. Tble IV. Comprison of Rmsy scores between two groups (men ± SD). Group Cse Before opertion 0.5 h fter opertion 12 h fter opertion 24 h fter opertion Tretment group ± ± ± ±0.19 Control group ± ± ± ±0.12 Compred with the tretment group, P<0.05. ws significntly higher thn tht of the tretment group (P<0.05), with sttisticl significnce (Tble II). Comprisons of serum IL-6, TNF-α nd CRP levels in ptients between two groups. In the tretment group, the levels of IL-6, TNF-α nd CRP before tretment were 3.25±0.98, 16.27±2.21 pg/ml nd 4.45±0.32 mg/l, respectively; the levels of IL-6, TNF-α nd CRP t 0.5 h fter opertion were 70.56±3.21, 15.02±2.06 pg/ml nd 5.78±0.19 mg/l, respectively; nd the levels of the three indexes t 24 h fter opertion were 60.72±2.98, 19.72±2.34 pg/ml nd 3.21±0.12 mg/l, respectively. In the control group, the levels of the three indexes before opertion were 3.69±0.65, 16.83±3.01 pg/ml nd 4.29±0.18 mg/l, respectively; the levels of the three indexes t 0.5 h fter opertion were 90.56±3.65, 16.75±2.10 pg/ml nd 8.12±0.21 mg/l, respectively; nd the levels of the three indexes t 24 h fter opertion were 67.97±3.98, 18.98±2.03 pg/ml nd 4.54±0.32 mg/l, respectively. It ws found tht the levels of IL-6 in two groups were incresed t 0.5 nd 24 h fter opertion, nd the levels of IL-6 in the control group were significntly higher thn tht in the tretment group. The postopertive level of CRP ws higher thn tht before opertion, nd the postopertive level in the control group ws higher thn tht in the tretment group (Tble III). Comprison of Rmsy scores between two groups. The preopertive Rmsy scores of ptients in the tretment group nd the control group were 1.97±0.21 nd 1.98±0.15 points, respectively. The Rmsy scores 0.5 h fter opertion of ptients in two groups were 4.13±0.43 nd 2.59±0.18 points, respectively. The Rmsy scores t 12 h fter opertion of ptients in two groups were 2.34±0.17 nd 1.99±0.10 points, respectively. The Rmsy scores t 24 h fter opertion of ptients in two groups were 2.05±0.19 nd 2.06±0.12 points, Figure 1. Comprisons of the dosges of fentnyl in ptients between two groups. * P<0.05, compred with tretment group. respectively. The results showed tht the Rmsy scores of ptients in the tretment group were higher thn those in the control group t 0.5 nd 12 h fter opertion, nd the differences were significnt between the two groups (Tble IV). Chnges in levels of T lymphocyte subsets in ptients during periopertive period between two groups. The levels of T lymphocyte subsets hd no difference between the two groups t the first time point. The CD3 + T, CD4 + T, CD4 + T/CD8 + T, Th1 nd Th1/Th2 in two groups were lower t T2 nd T3 thn those t T0, nd the Treg vlues t T2 nd T3 were significntly higher thn those t T0. It ws lso found tht the indexes of CD3 + T, CD4 + T, CD4 + T/CD8 + T, Th1 nd Th1/Th2 in the tretment group were lower thn those in the control group, nd the Treg vlue ws higher thn tht in the control group (P<0.05) (Tble V). Comprison of the dosges of fentnyl in ptients between two groups. The fentnyl dosges during opertion nd fter opertion in the tretment group were 0.63±0.11 nd

4 7156 WANG nd LI: EFFECTS OF DEXMEDETOMIDINE ON PATIENTS WITH COLON CARCINOMA Tble V. Chnges in levels of T lymphocyte subsets in ptients during periopertive period between two groups (men ± SD). Group Time CD3+ T (%) CD4 + T (%) CD8 + T (%) CD4 + T/CD8 + T Th1 (%) Th2 (%) Th1/Th2 Th17 (%) Treg (%) Tretment group T0 61.9± ± ± ± ± ± ± ± ±1.1 T1 (6 hours) 58.3± ± ± ± ± ± ± ± ±1.0 T2 (1 dy) 57.2± ± ± ± ± ± ± ± ±1.2 T3 (2 dys) 58.4± ± ± ± ± ± ± ± ±1.2 T4 (3 dys) 60.1± ± ± ± ± ± ± ± ±1.0 Control group T0 61.2± ± ± ± ± ± ± ± ±1.2 T1 (6 hours) 59.4± ± ± ± ± ± ± ± ±1.3 T2 (1 dy) 56.2±9.6,b 40.1±6.4,b 17.8± ±0.8,b 23.0±3.8,b 2.2± ±2.9,b 1.9± ±1.3,b T3 (2 dys) 53.9±7.9,b 40.2±6.3,b 17.9± ±0.9,b 23.7±3.6,b 2.5± ±2.7,b 2.2± ±1.3,b T4 (3 dys) 60.9± ± ± ± ± ± ± ± ±1.2 Compred with tht t T0, P<0.05; b compred with the tretment group, P< ±0.09 mg respectively, nd the fentnyl dosges during opertion nd fter opertion in the control group were 0.98±0.21 nd 0.99±0.19 mg respectively, suggesting tht the fentnyl dosge whether during opertion or fter opertion in the tretment group ws lower thn tht in the control group (P<0.05) (Fig. 1). Discussion Inflmmtion, s physiologicl disese, often occurs in the body. When inflmmtion occurs in the body, it will led to chnges in blood vessels, cells nd other tissues (11,12). Clinicl studies hve found tht the use of nesthetics in the body cn ct on inflmmtory fctors, such s mononucler mcrophges, nd lso ffect inflmmtory meditors (13,14). The reserch on nti-inflmmtory effect of ll nesthetics is bsed on vriety of inflmmtory fctors. The most widely used inflmmtory fctors re IL-6, TNF-α nd IL-8. IL-6 nd IL-8 re produced by mononucler mcrophges in the body, while TNF-α is secreted by neutrophils. A vriety of inflmmtory fctors cn ffect the neutrophil chemotxis nd induce llergic rections, leding to chemotxis of T cells, which cn promote the immune response in the body to certin extent (15,16). NF-κB is key nucler trnscription fctor in the body nd plys n importnt role in the immune nd inflmmtion processes. When the body is stimulted by inflmmtory fctors, IκB, n inhibitor of NF-κB, will be degrded, leding to over-secretion of NF-κB in the body; the excessive NF-κB will be trnsferred into the nucleus, leding to gene expression (17). ICAM-1 is widely used in ntigen production nd leukocyte infiltrtion process, nd it is widely distributed in lymphocytes. As kind of multifunctionl dhesion molecule, it is lso involved in the process of body immunity. T cell subsets hve been cliniclly proven to be importnt indexes of immune disorders of the body, nd Treg is subset of T cells tht cn inhibit the immune response in cncer ptients. Clinicl studies hve found tht dexmedetomidine cts on the blue plque in brin, which cn reduce norepinephrine secretion, inhibit oxidtive stress, nd inhibit the occurrence of inflmmtion (18-20). In this study the degree of the increse in the inflmmtory fctors t 0.5 nd 24 h fter opertion in the tretment group ws significntly lower thn those in the control group (P<0.05). Ptients in two groups hd the sme fctor levels before opertion, indicting tht the dexmedetomidine nesthesi cn significntly inhibit the secretion of inflmmtory fctors nd inhibit the relese of inflmmtory meditors. Clinicl studies hve found tht when dexmedetomidine tkes effect, the ptient's centrl nervous system receptors will be ffected, nd the norepinephrine will be inhibited, leding to less stress response in ptients nd decresed secretion of ctecholmine in drenergic receptor nd glucocorticoid receptor in ptients, which ultimtely inhibits the production of inflmmtory fctors. In this study, it ws lso found tht the sedtion in the tretment group ws better thn tht in the control group (P<0.05). Dexmedetomidine cn ct on the nerve center of the body to reduce the relese of norepinephrine nd increse the threshold of excitement.

5 ONCOLOGY LETTERS 15: , In conclusion, the ppliction of dexmedetomidine in ptients receiving rdicl opertion of colon crcinom hs better clinicl effect, which cn reduce the production of inflmmtory fctors, decrese the inhibition of T lymphocyte subsets, nd lower the impct on NF-κB in peripherl blood mononucler cells, with higher clinicl therpeutic vlue. Acknowledgements Not pplicble. Funding No funding ws received. Avilbility of dt nd mterils All dt generted or nlyzed during this study re included in this published rticle. Authors' contributions KW designed the study nd prepred the mnuscript. CL collected nd nlysed the dt. All uthors red nd pproved the finl mnuscript. Ethics pprovl nd consent to prticipte This study ws pproved by the Ethics Committee of Jining No. 1 People's Hospitl (Jining, Chin). Signed written informed consents were obtined from ll ptients or their gurdins before the study. Consent for publiction Not pplicble. Competing interests The uthors declre tht they hve no competing interests. References 1. Wlker SM, Grfe M nd Yksh TL: Intrthecl clonidine in the neontl rt: Dose-dependent nlgesi nd evlution of spinl poptosis nd toxicity. Anesth Anlg 115: , Ozcengiz D, Unlügenç H, Güneş Y nd Krcer F: The effect of dexmedetomidine on bispectrl index monitoring in children. Middle Est J Anesthesiol 21: , Bnnister CF, Brosius KK, Sigl JC, Meyer BJ nd Sebel PS: The effect of bispectrl index monitoring on nesthetic use nd recovery in children nesthetized with sevoflurne in nitrous oxide. Anesth Anlg 92: , Li HL, She SZ, Yn Y nd Zhu SM: Effect of dexmedetomidine on bispectrl index nd uditory evoked potentil index during nesthesi with trget controlled infusion of propofol nd remifentnyl. Zhejing D Xue Xue Bo Yi Xue Bn 39: 84-88, 2010 (In Chinese). 5. Ishibshi C, Hyshid M, Sugsw Y, Ymguchi K, Tomit N, Kjiym Y nd Ind E: Effects of dexmedetomidine on hemodynmics nd respirtion in intubted, spontneously brething ptients fter endoscopic submucosl dissection for cervicl esophgel or phryngel cncer. J Anesth 30: , Lin H, Frkls I, Smpson C, Sffle JR nd Cochrn A: Use of dexmedetomidine for sedtion in criticlly ill mechniclly ventilted peditric burn ptients. J Burn Cre Res 32: , Zho XN, Rn JH, Bjrchry AR nd M MY: Effect of different doses of dexmedetomidine on medin effective concentrtion of propofol for nesthesi induction: A rndomized controlled tril. Eur Rev Med Phrmcol Sci 20: , Vlenz G, Akeju O, Pvone KJ, Citi L, Hrtnck KE, Smpson A, Purdon PL, Brown EN nd Brbieri R: Instntneous monitoring of hert bet dynmics during nesthesi nd sedtion. J Comput Surg 1: 1-18, Wlker SM, Howrd RF, Key KA nd Fitzgerld M: Developmentl ge influences the effect of epidurl dexmedetomidine on inflmmtory hyperlgesi in rt pups. Anesthesiology 102: , Dong W, Chen MH, Yng YH, Zhng X, Hung MJ, Yng XJ nd Wng HZ: The effect of dexmedetomidine on expressions of inflmmtory fctors in ptients with rdicl resection of gstric cncer. Eur Rev Med Phrmcol Sci 21: , Chu NJ, Armstrong TD nd Jffee EM: Nonvirl oncogenic ntigens nd the inflmmtory signls driving erly cncer development s trgets for cncer immunoprevention. Clin Cncer Res 21: , Smit MA, Jffee EM nd Lutz ER: Cncer immunoprevention - the next frontier. Cncer Prev Res (Phil) 7: , Kostopngiotou G, Sidiropoulou T, Pyrsopoulos N, Pretto EA Jr, Pndzi A, Mtsot P, Arkdopoulos N, Smyrniotis V nd Tzkis AG: Anesthetic nd periopertive mngement of intestinl nd multiviscerl llogrft recipient in nontrnsplnt surgery. Trnspl Int 21: , Nesković V: Preopertive ssesment of the immunocompromised ptient. Act Chir Iugosl 58: , Remotti H, Subrmnin S, Mrtinez M, Kto T nd Mgid MS: Smll-bowel llogrft biopsies in the mngement of smllintestinl nd multiviscerl trnsplnt recipients: Histopthologic review nd clinicl correltions. Arch Pthol Lb Med 136: , Yuki K, Sorino SG nd Shimok M: Sedtive drug modultes T-cell nd lymphocyte function-ssocited ntigen-1 function. Anesth Anlg 112: , Alonso-Aris R, Moro-Grcí MA, Vidl-Cstiñeir JR, Solno- Jurriet JJ, Suárez-Grcí FM, Coto E nd López-Lrre C: IL-15 preferentilly enhnces functionl properties nd ntigen-specific responses of CD4 + CD28 null compred to CD4 + CD28 + T cells. Aging Cell 10: , Cn M, Gul S, Bekts S, Hnci V nd Acikgoz S: Effects of dexmedetomidine or methylprednisolone on inflmmtory responses in spinl cord injury. Act Anesthesiol Scnd 53: , Fng B, Li XQ, Bi B, Tn WF, Liu G, Zhng Y nd M H: Dexmedetomidine ttenutes blood-spinl cord brrier disruption induced by spinl cord ischemi reperfusion injury in rts. Cell Physiol Biochem 36: , Bicer C, Esmoglu A, Akin A nd Boyci A: Dexmedetomidine nd meperidine prevent postnesthetic shivering. Eur J Anesthesiol 23: , This work is licensed under Cretive Commons Attribution-NonCommercil-NoDerivtives 4.0 Interntionl (CC BY-NC-ND 4.0) License.