马燕花 杨少军 师霞 邱晓青 徐三朋

摘要：目的 观察慈菇消脂丸对非酒精性脂肪性肝炎（NASH）大鼠肝脏脂质代谢及抗氧化能力的影响，探讨其相关作用机制。方法 SD大鼠随机分为正常组、模型组、阳性药组和中药高、中、低剂量组。采用高脂饲料饲喂大鼠建立NASH模型，造模同时给予相应药物干预。造模12周，实验大鼠全部处死，取大鼠肝脏和血清。检测血清丙氨酸氨基转移酶（ALT）、天冬氨酸氨基转移酶（AST）、三酰甘油（TG）、总胆固醇（TC）、总超氧化物歧化酶（T-SOD）、低密度脂蛋白胆固醇（LDL-C）、丙二醛（MDA）、谷胱甘肽过氧化物酶（GSH-Px）、游离脂肪酸（FFA）及肝组织匀浆T-SOD、MDA、GSH-Px、FFA，HE染色观察肝组织病理形态，透射电镜观察肝细胞超微结构，油红O染色观察肝细胞脂肪变性。结果 造模大鼠肝组织呈中重度脂肪变性并伴有炎症细胞浸润。与正常组比较，模型组大鼠肝湿重、肝指数和血清ALT、AST、TG、TC、LDL-C、MDA、FFA及肝组织匀浆MDA、FFA均明显升高（P<0.05，P<0.01），血清及肝组织匀浆T-SOD、GSH-Px明显降低（P<0.05，P<0.01）；与模型组比较，中药高剂量组血清ALT、AST、TG、TC、LDL-C、MDA、FFA明显降低，肝组织匀浆MDA、FFA明显降低（P<0.05，P<0.01），血清及肝组织匀浆T-SOD、GSH-Px明显升高（P<0.01）。病理观察显示，与模型组比较，中药各剂量组大鼠肝小叶内空泡样变、脂肪样变减少，炎性细胞浸润明显改善。结论 慈菇消脂丸能明显改善模型大鼠肝功能及血脂水平，提高肝脏抗氧化能力，减轻脂质过氧化损伤，达到防治NASH的目的。

关键词：非酒精性脂肪性肝炎；慈菇消脂丸；脂毒性；氧化应激；大鼠

DOI：10.3969/j.issn.1005-5304.2018.01.011

中图分类号：R285.5 文献标识码：A 文章编号：1005-5304（2018）01-0048-06

Effects of Cigu Xiaozhi Pills on Lipotoxicity and Oxidative Stress

in Rats with Non-alcoholic Steatohepatitis

MA Yan-hua1， YANG Shao-jun2， SHI Xia1， QIU Xiao-qing3， XU San-peng1

1. Gansu University of Chinese Medicine， Lanzhou 730000， China；

2. Beihai Traditional Chinese Medicine Hospital， Beihai 536000， China；

3. Affiliated Hospital of Gansu University of Chinese Medicine， Lanzhou 730000， China

Abstract： Objective To explore the effects of Cigu Xiaozhi Pills on lipotoxicity and oxidative stress in rats with non-alcoholic steatohepatitis （NASH）； To discuss relevant mechanism of action. Methods SD rats were divided into six groups randomly： normal control group， model group， positive medicine group， Cigu Xiaozhi Pills high-， medium-， and low-dose groups. NASH model was established by feeding rats with high fat diet for 12 weeks. At the same time， the model rats were given medicine intervention. At the end of 12 weeks， all the experimental animals were killed and the liver and serum were taken. Serum samples were taken for detection of ALT， AST， TG， TC， T-SOD， LDL-C， MDA， GSH-Px and FFA. Liver tissues were taken for detection of T-SOD， MDA， GSH-Px and FFA. The liver histopathological changes were observed under microscope with HE staining. The ultrastructure of liver cells was observed by transmission electron microscope. The fatty degeneration of liver cells was observed by oil red O staining. Results Liver histopathological examination showed that the liver tissue of model group showed moderate to

基金項目：国家自然科学基金地区基金（81560753）

severe steatosis and inflammatory cell infiltration. Compared with normal control group， rat liver wet weight， liver index， ALT， AST， TG， TC， LDL-C， MDA and FFA in serum， and FFA and MDA in liver homogenate in model group significantly increased （P<0.05， P<0.01）， while T-SOD and GSH-Px activity in serum and liver homogenate significantly decreased （P<0.05， P<0.01）. Compared with model group， Cigu Xiaozhi Pills high-dose group could significantly decrease the elevation of serum ALT， AST， TG， TC， LDL-C， MDA and FFA （P<0.05， P<0.01）， but increase T-SOD and GSH-Px activity in serum and liver tissue （P<0.01）. The pathological section showed that： compared with model group， the hepatic lobule vacuolar degeneration and fatty degeneration were significantly reduced in Cigu Xiaozhi Pills high-， medium- and low-dose groups， and the inflammatory cell infiltration was improved. Conclusion Cigu Xiaozhi Pills can obviously improve liver function and blood lipid of NASH rat model induced by high-fat diet， enhance antioxidant capacity， reduce lipid peroxidation and achieve the purpose of prevention and treatment of NASH.

Keywords： non-alcoholic steatohepatitis； Cigu Xiaozhi Pills； lipotoxicity； oxidative stress； rats

非酒精性脂肪性肝炎（non-alcoholic steatohepatitis，NASH）作为非酒精性脂肪性肝病（nonalcoholic fatty liver disease，NAFLD）的临床病理类型之一，由于其可进展为肝纤维化、肝硬化甚至肝癌等终末期肝病，一直备受重视。NASH发病机制复杂，涉及脂代谢紊乱、胰岛素抵抗、肝脂质过氧化增加、细胞因子异常等多个相互关联的病理生理环节。研究发现，NASH发生、发展过程中肝细胞脂毒性凋亡是其重要特征，并参与整个发病过程[1]。游离脂肪酸（FFA）在NASH的发生中发挥重要作用[2]。……