西维来司钠对重症急性胰腺炎大鼠肝细胞凋亡及B-淋巴细胞／白血病-2／bax表达的影响  

Effects of sivelestat on hepatocyte apoptosis and B lymphocytes/leukemia-2/bax expression in rats with severe acute pancreatitis

作　　者：王琦[1] 沈世强[1] 林福生[1] 邹力[1] 

机构地区：[1]武汉大学人民医院普通外科,430060

出　　处：《中华实验外科杂志》2012年第6期1127-1130,F0004,共5页Chinese Journal of Experimental Surgery

摘　　要：目的观察西维来司钠（Sivelestat）对重症急性胰腺炎（SAP）大鼠肝细胞凋亡及B-淋巴细胞／白血病-2（bcl-2）／bax基因表达的影响，并探讨其机制。方法健康雄性SD大鼠54只，随机分为C组（对照组）、P组（SAP组）、S组（SAP＋Sivelestat治疗组），每组18只。c组为假手术组，P组大鼠以4％牛黄胆酸钠胆胰管逆行注射制造重症急性胰腺炎模型，s组造模后立即给予Sivelestat[0．2mg／（kg·h）]尾静脉注射治疗。3组大鼠术后3、6、12h分别取6只检测血清中性粒细胞弹性蛋白酶（NE）含量；取肝组织测定丙二醛（MDA）及超氧化物歧化酶（SOD）含量；原位末端标记（TUNEL）法检测造模后大鼠肝细胞凋亡并计算凋亡指数（AI）；流式细胞术方法测定肝细胞凋亡率；Westernblot法检测造模后12hbcl-2／bax基因表达。结果与c组比较，各时点P组大鼠血清NE含量[（5．62±1．70）、（6．83±2．01）、（10．88±3．72）ug／L]、肝细胞凋亡指数（11．4±1．1、15．3±1．1、21．3±1．2）及细胞凋亡率均明显升高；肝组织内MDA含量升高[（9．13±1．32）、（11．62±3．71）、（13．57±3．29）nmol／mg]，SOD含量下降[（154．00±22．38）、（138．05±29．48）、（122．63±28．71）U／mg]；肝组织bcl-2表达减少，bax表达增多。与P组比较，各时点s组大鼠血清NE含量[（3．57±2．30）、（4．11±2．16）、（6．66±2．69）ug/L]、肝细胞凋亡指数（8．1±0．7、11．2±0．8、15．1±1．0）及细胞凋亡率均有明显降低；肝组织内MDA含量降低[（5．75±0．86）、（7．95±3．01）、（9．77±3．45）nmol／mg]而SOD含量升高[（187．12±37．39）、（179．23±44．59）、（163．55±25．79）U／mg]；肝组织bcl-2表达增多而bax表达下降。结论西维来司钠可抑制SAP大鼠肝细胞凋亡，具体机制可能与其拈抗NE及氧自由基从而提高bcl-2／bax比值有关。Objective To investigate the effects of sivelestat on hepatocyte apoptosis and B lymphocytes/leukemia-2 （bcl-2）/bax expression of rats with severe acute pancreatitis （SAP）, and the potential mechanism. Methods Fifty-four male Sprague-Dawley rats were equally divided into three groups randomly： group C （control group）, group P （SAP group） and group S （SAP ＋ sivelestat group）. The SAP models were induced by retrograde injection of 4% sodium taurocholate into bilopancreatic duct of SD rats. Group C rats were injected with isometric physiological saline. Group P rats were treated with sivelestat [0. 2 mg/（kg·h） ] via the caudal vein after models were induced. Serum levels of neutrophil elastase （NE） , malondialdehyde （MDA） and superoxide dismutase （SOD） activity of liver tissue were measured 3, 6, and 12 h after operation. Hepatocytes apoptosis was detected by using terminal deoxynuceotidy transferase mediated dUTP nick end labeling （TUNEL） and apoptosis index （AI） was calculated. Hepatocellular apopotosis rate was examined by using flow cytometer. The expression of bcl-2 and bax was detected by using Western blotting. Results As compared with group C, the serum levels of NE [ （5.62 ± 1.70）, （6. 83± 2. 01 ）, （ 10. 88± 3.72） ug/L], hepatocytes AI （ 11.4 ± 1.1, 15.3 ± 1.1,21.3 ± 1.2） and apopotosis rate were increased at 3rd, 6th, and 12th h after operation in the group P; the MDA activity of liver tissue [ （9. 13 ± 1.32）, （11.62 ±3.71）, （13.57 ±3.29） nmol/mg] was increased and the SOD activity [ （ 154. 00 ± 22. 38 ）, （ 138. 05 ±29.48 ）, （ 122. 63 ± 28. 71 ） U/mg ] was reduced; the expression levels of bcl-2 were decreased and those of bax were increased. As compared with group P, the serum levels ofNE [ （3.57 ±2. 30）, （4. 11 ±2. 16）, （6. 66 ±2.69） ug/L] , hepatocytes AI （8.1±0.7, 11.2±0.8, 15.1±1.0） and apopotosis rate, the MDA activity [（5.75 ±0.86）, （7.95 ±3.01）, （9.77 ± 3.45） nmo

关 键 词：西维来司钠 胰腺炎 肝损害 脱噬作用 

分 类 号：R657.51[医药卫生—外科学]