摘要
目的探讨奥曲肽对胰腺炎相关性腹水(PAAF)诱导的大鼠肝细胞凋亡的保护作用及其相关机制。方法以PAAF诱导的大鼠肝损伤模型(B组)为研究对象,监测4、7h血清肝功能酶学指标(ALT、AST)、总胆红素(TBiL)、淀粉酶(AmYL)及转化生长因子(TGF)β1浓度。同时对胰腺、肝组织进行组织学观察;TUNEL法流式细胞术定量检测肝细胞凋亡情况,以及应用奥曲肽后(C组)对上述指标的变化。对比评估B组与急性坏死性胰腺炎模型(ANP组)胰腺损伤程度。结果B组各血清学指标均比空白对照组(A组)显著升高(P<0.01);C组上述各指标显著下降(P<0.01);ANP组与B组相比,7h时间点AmYL浓度明显升高(P<0.01)。PAAF诱导7h后(20.13±3.84)%的肝细胞发生凋亡,其中(49.04±1.44)%细胞生长停滞在G2/M期。电镜(TEM)下可见典型的晚期凋亡肝细胞;ANP组胰腺损伤程度明显重于B组。结论(1)TGFβ1在肝细胞增殖(G2/M)期诱导其凋亡损伤;(2)奥曲肽通过抑制TGFβ1在肝脏的表达而对PAAF诱导的大鼠肝细胞凋亡具有良好的保护作用;(3)PAAF诱导的大鼠肝损伤模型中的胰腺病变明显轻于ANP时的胰腺病变。
Objective To investigate the protective effects of octreotide on hepatocytes apoptosis induced by pancreatitis associated ascitic fluid （PAAF） in rats and explore its intrinsic mechanism. Methods Liver injury models induced by PAAF（group B） was used. The levels of ALT, AST, TbiL, AmYL and TGF-β1 in serum were determined in 4 h and 7 h. Liver and pancreas samples were analyzed for histopathology. The apoptosis ratio of hepatocytes and its cell cycle distribution were detected by using flow cytometry （FCM） with terminal deoxynucleotidyl transferase biotin-dUTP nick end labelling （TUNEL） method. Meanwhile the influences of Octreotide on those indexes （group C） were also observed. Otherwise the contrast degree of pancreas injury was evaluated between group B and acute necrotizing pancreatitis models （group ANP）. Results The levels of all indexes in serum were increased significantly in group B as compared with those in control group （group A）（P〈 0.01） and group C （P〈0.01）.As compared with group B, the levels of AmYL in serum were increased significantly in group ANP too （P〈0.01）.About （20.13±3.84）% hepatocytes had apoptosis in 7 h in group B and about （49.04±1.44）% apoptotic hepatocytes growth ceased in the G2/M stage. Classical non-vlable apoptotic liver cells were indicated through TEM in group B. The pathological changes of pancreas acinic cells in group ANP were more seriously than in group B. Conclusion（ 1）TGF-β1 can induce hepatocytes apoptosis at G2/M stage. （2）Octreotide has well protective effects on hepatocytes apoptosis induced by PAAF thought inhibiting the expression of TGF-β1 in the liver. （3） The pathological changes of pancreas acinic cells in group B were milder than in group ANP.
出处
《中华实验外科杂志》
CAS
CSCD
北大核心
2005年第8期947-949,共3页
Chinese Journal of Experimental Surgery
关键词
奥曲肽
大鼠
肝细胞
细胞凋亡
胰腺炎相关性腹水
Pancreatitis
Ascitic fluid
Hepatocytes
Apoptosis
Transforming growth factor -β
Octreotide
