丹参素和泮托拉唑对肝硬化大鼠肝部分切除术后肝再生的影响研究

Hepatocyte regeneration and effects of tanshinol, pantoprazole after partial hepatectomy in rats with liver cirrhosis

目的以肝硬化大鼠为动物模型,研究药物对肝硬化大鼠肝部分切除术后肝再生的影响。方法取健康的Wistar雄性大鼠64只,以60%CCl4油溶液0.3ml/100g皮下注射,同时饮用5%酒精溶液,45d后制成肝硬化动物模型。模型大鼠随机分为4组,16只/组。全麻下均行左、中叶肝切除术。术后各组按以下方案处理:对照组皮下注射生理盐水1mg·kg-1·d-1,丹参素组腹腔注射18mg·kg-1·d-1,泮托拉唑组皮下注射0.2mg·kg-1·d-1,两药合用组同时给予丹参素(tanshinol)腹腔注射18mg·kg-1·d-1,泮托拉唑(pantoprazole)皮下注射0.2mg·kg-1·d-1,连续给药2周,抽取静脉血样,取肝脏组织,检测肝功能、有丝分裂指数(MI)、增生细胞核抗原(PCNA)、细胞核DNA含量。结果丹参素组、泮托拉唑组及两药合用组MI、PCNA阳性染色细胞量、细胞核DNA含量均高于对照组(P<0.05),两药合用组MI、PCNA阳性染色细胞量、细胞核DNA含量均高于丹参素组、泮托拉唑组(P<0.05),但各组间肝功能变化无明显差异。结论丹参素、泮托拉唑及两药合用均对肝硬化大鼠肝部分切除术后肝细胞再生有促进作用。

Objective To study the regenerative capability of liver after partial hepatectomy and the effects of tanshinol and pantoprazole on the hepatic regeneration in cirrhotic rats. Methods Liver cirrhosis was induced by the injection of 60% CCl4 0.3 ml/100 g body weight each time. At the same time, all rats received 5% alcohol solution as the only water source. After 45 days, cirrhosis models were established. Cirrhotic rats were randomly separated into four groups (n=16), and each rat underwent 70% hepatectomy. The drugs were administrated on the day of the operation and lasted for two weeks. Group A was given 0.9% NS, subcutaneous (SC.) 1 mg·kg-1·d-1 as control; group B, tanshinol 18 mg·kg-1·d-1, intraperitoneal; group C, pantoprazole 0.2 mg·kg-1·d-1, subcutaneous; group D, tanshinol 18 mg·kg-1·d-1, intraperitoneal and pantoprazole 0.2 mg·kg-1·d-1 subcutaneous. Two weeks after treatment, group A rats were killed, and blood was taken from the inferior vena cava for the determination of ALT and AST. The liver specimens were examined with a microscope examination and determination of MI (mitotic index), PCNA (proliferative cell nuclear antigen) and contents of DNA in cell nucleus were determined. Results MI, PCNA and the contents of DNA in cell nucleus were significant higher in tanshinol group, pantoprazole group and the combination of tanshinol plus pantoprazole group than those in control (P<0.05). MI, PCNA and DNA contents in cell nucleus in tanshinol plus pantoprazole group was higher than those of in tanshinol group or in pantoprazole group. But there was no difference in liver function alternation. Conclusion The study suggests that tanshinol, pantoprazole or tanshinol plus pantoprazole enhance the cirrhotic liver regeneration after hepatectomy. Combination of pantoprazole with tanshinol could enhance more liver cell regeneration than the others.