肾宝组方及其拆方对慢性肝损伤大鼠肝脏功能及病理形态的影响

Effects of Shenbao Formulas and its Disassembled Prescription on the Liver Functions and Morphology of Rats with Chronic Liver Injury

目的:考察肾宝组方及其拆方长期大剂量给药对慢性肝损伤大鼠肝脏功能及肝脏病理形态的影响,为有基础肝病或肝功能不全患者临床长期用药的安全性提供参考。方法:SD雄性大鼠共300只,随机分成正常对照组,模型组,肾宝片高、中、低剂量组,制何首乌高、低剂量组,淫羊藿高、低剂量组,补骨脂高、低剂量组,制何首乌+淫羊藿+补骨脂高、低剂量组,全方不含制何首乌+淫羊藿+补骨脂高、低剂量组,每组20只。正常对照组腹腔注射生理盐水,其余各组采用10%CCl4橄榄油灌胃,每周2次,共12周,制备慢性肝损伤模型。4周后,各组灌胃给予相应药物,正常组和模型组灌胃蒸馏水,每日1次,连续12周,停药恢复4周。给药期和恢复期观察各组大鼠一般状况,每周测定大鼠体重。在给药期结束和恢复期结束,各组分别检测肝功能生化指标、氧化应激水平和肝脏组织病理学检查。结果:与模型组相比,肾宝组方对CCl4慢性肝损伤大鼠的肝功能生化指标、肝组织氧化应激水平、组织病理形态学等均无加重现象,反而在给药12周后明显降低肝损伤大鼠的血清ALT、AST活性及肝脏MDA含量,同时明显增加SOD水平,且肝脏组织病理评分也较模型组有降低趋势。结论:肾宝处方组成中虽然含有肝毒性中药,但是全方组方合理,可以起到减轻肝毒性的作用,即使已有基础性肝病或肝功能不全患者长时间服用也不会增加肝脏毒性反应,表明其临床使用的安全可靠。

Objective:To observe the effects of Shenbao formulas and its disassembled prescription on liver functions and morphology in rats with chronic liver injury after a long-term and large doses administration,in order to evaluate the safety of a long-term treatment of Shenbao formulas for patients with liver insufficiency or liver disease.Methods:The 300 SD rats were randomly divided into normal group,model group,high,middle,low dose groups of Shenbao formulas,high,low dose groups of Radix Polygoni multiflori praeparata(PM),high,low dose groups of Epimedium koreanum Nakai(EK),high,low dose groups of Psoralea corylifolia(PC),high,low dose groups of PM+EK+PC,high,low dose groups of the whole Shenbao decoction without PM+EK+PC,with 20 rats in each group.The rats of the normal group were injected with normal saline,and the others were intragastrically administrated with 10%CCl4 twice a week for 12 weeks to establish chronic injury model.After 4 weeks,each administration group was treated with the corresponding drug once daily for 12 weeks,which the normal group and model group were instead of distilled water,and then drugs were stopped for 4 weeks for observation.The routine examination,and body weight changes were observed during the dosing period and recovery phase.The biochemical indexes,organ coefficient and histopathology of the liver were examined after dosing period and recovery phase.Results:Compared with the model group,there was no obvious aggravation of Shenbao formulas at different doses on liver function biochemical indexes,oxidative stress level and histopathological morphology of liver tissue in rats with chronic liver injury.On the contrary,after 12 weeks of Shenbao formulas administration,the levels of ALT and AST in serum and the content of MDA in liver of rats were significantly decreased,and the level of SOD was significantly increased,and the liver histopathological score was decreased compared with that of the model group.Conclusion:Although the prescription composition of Shenbao formulas contains hepatotoxic Chinese medicine, the whole decoction can play a reasonable role in alleviating hepatotoxicity, even if the patients with underlying liver disease or liver insufficiency take it for a long time, it will not increase hepatotoxic reactions, indicating that its clinical use is safe and reliable.