精氨酸对梗阻性黄疸大鼠肝损伤的保护作用及其对肝细胞凋亡的影响

Observation of arginine’s protection from hepatic injury and its effect on hepatic cell apoptosis in the rats with obstructive jaundice

目的探讨梗阻性黄疸时精氨酸是否对肝脏具有保护作用及其对肝细胞凋亡的影响。方法Wistar大鼠42只随机分为3组:A组为假手术组、B组为梗阻性黄疸组、C组为精氨酸治疗组;B组和C组采取双重结扎大鼠胆总管制作梗阻性黄疸模型,C组术后第1天开始每天腹腔注射精氨酸500mg/(kg·d),分别于术后第7天和第14天取材,采集鼠血清检测TBIL、DBIL、ALT、AST;大鼠肝脏组织进行HE染色切片观察组织形态,电镜观察胞内形态并对组织切片应用Bax、Bcl-2试剂盒行免疫组化染色。结果与A组大鼠相比,B组大鼠血清胆红素和转氨酶明显增高,肝细胞损伤不断加重并出现显著凋亡改变,随着胆总管结扎时间的延长而更加明显。应用精氨酸治疗的C组大鼠,其肝功能和肝脏组织病理学改变较B组轻。B组和C组大鼠肝组织中Bax、Bcl-2蛋白表达均随时间而增多,但B组Bax表达增多较明显,而C组Bcl-2蛋白表达增多较明显。结论精氨酸对梗阻性黄疸大鼠肝脏有保护作用,可能是通过上调肝脏组织Bcl-2蛋白表达,下调肝脏组织Bax蛋白的表达减少细胞凋亡来实现的。

Objective To explore whether arginine could lighten the hepatic dysfunction of rat with obstructive jaundice （OJ） and the influence of arginine on hepatic cell apoptosis. Methods A total of 42 adult Wistar rats were studied. They were divided into three groups： the sham operation group （A group）, the OJ group （B group） and the group of OJ rats administered arginine （C group）. The B and C group were established by double-ligating bile duct （BDL）. Abdomenal injections of arginine （500 mg/kg·d） postoperatvely was administered daily in C group. Three groups of rats were sacrificed after 1 and 2 weeks of postoperation, respectively. The levels of serum total bilirubin （TBIL） , direct bilirubin （DBIL）, alanine aminotransferase （ALT） and aspartate aminotransferase （AST） were tested and the tissue’s histopathology and ultrastructure changes were observed; the immunohistochemical technique was used for detecting the Bcl-2 and Bax protein expression. Results With the time of BDL extending, the values of serum ALT, AST, TBIL and DBIL were increased and the value of B group was higher than that of A group （P〈0.05）; following that cell apoptosis increased apparently in hepatic tissue. Compared with B group, the injury degree of hepatic function and histopathology of changes in C group were decreased. With the time extending, the Bcl-2 and Bax protein of both B and C group were increased. The Bcl-2 was increased more evidently in C group, just like Bax in B group. Conclusion Arginine can ease the degree of hepatic functional injury, for it may decrease cell apoptosis by up-regulating the expression of Bcl-2 and down-regulating the expression of Bax in hepatic tissue.