| 健脾消脂汤增强自噬对非酒精性脂肪性肝病小鼠肝脏脂肪变改善作用的实验研究 |
| Enhancing Autophagy with Jianpi Xiaozhi Decoction Ameliorates Hepatic Steatosis in a Mouse Model of Non-Alcoholic Fatty Liver Disease |
| DOI： |
| 中文关键词: 非酒精性脂肪性肝病 健脾消脂汤 自噬 Beclin1 LC3B |
| 英文关键词: Non-alcoholic fatty liver disease Jianpi Xiaozhi Decoction Autophagy Beclin1 LC3B |
| 基金项目:国家自然科学基金(82274468)；安徽中医药领军人才建设项目(中医药发展秘〔2018〕23 号); 安徽省名中医及基层名中医工作室建设项目(中医药发展秘〔2021〕8 号) |
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| 中文摘要: |
| 目的 观察健脾消脂汤(Jianpi Xiaozhi decoction, JPXZ)对非酒精性脂肪性肝病(Non-alcoholic fatty liver disease,NAFLD)小鼠的肝脏脂肪变的改善作用,以及对自噬相关蛋白Beclin1、LC3B表达的影响。方法 将24只小鼠分为正常组、模型组、多烯磷脂酰胆碱组(Polyene phosphatidyl choline,PPC)、JPXZ低剂量组(JPXZ-L),JPXZ中剂量组(JPXZ-M),JPXZ高剂量组(JPXZ-H),每组4只。正常组给予普通饲料,其余予以高脂饮食饲养建立NAFLD模型,建模成功后以JPXZ低、中、高剂量分别进行灌胃,连续28天。检测小鼠血清丙氨酸氨基转移酶(ALT)、谷氨酸氨基转移酶(AST)和碱性磷酸酶(ALP)、甘油三酯(TG)、胆固醇(TC)、低密度脂蛋白(LDL-C),高密度脂蛋白(HDL-C)水平。HE和油红O染色观察小鼠肝脏病理形态改变及脂滴沉积,电镜观察细胞内脂滴的沉积及自噬小体、自噬溶酶体的变化,qRT-PCR方法检测小鼠肝组织中Beclin1、LC3B的mRNA表达水平的变化。结果 与正常组比较,模型组小鼠血清ALT、AST、ALP、TG、TC、LDL-C水平明显升高(P<0.01),HDL-C水平明显下降(P<0.001),HE染色显示模型组肝细胞炎性细胞浸润明显,油红染色显示细胞内脂滴明显增多,电镜下肝细胞内脂滴堆积,可见少量自噬溶酶体,qRT-PCR显示Beclin1、LC3B的mRNA的表达明显下调(P<0.001)。与模型组相比,PPC组和JPXZ中、高剂量组的ALT、AST、TG、TC、LDL-C水平均明显下降(P<0.05),HE染色显示肝脏炎性细胞浸润减轻,脂肪空泡减少,油红染色显示肝细胞内脂滴沉积减少,且随着中药干预浓度的增大改善更为明显,qRT-PCR显示Beclin1、LC3B的mRNA的表达明显上调(P<0.05)。结论 健脾消脂汤可能通过增强自噬从而改善非酒精性脂肪性肝病小鼠肝细胞的脂肪变。 |
| 英文摘要: |
| Objective: To observe the ameliorative effects of Jianpi Xiaozhi Decoction (JPXZ) on hepatic steatosis in mice with non-alcoholic fatty liver disease (NAFLD) and its impact on the expression of autophagy-related proteins Beclin1 and LC3B. Methods: Twenty-four mice were divided into six groups (n=4 per group): the normal control group, the model group, the polyene phosphatidylcholine (PPC) group, the JPXZ low-dose (JPXZ-L) group, the JPXZ medium-dose (JPXZ-M) group, and the JPXZ high-dose (JPXZ-H) group. The normal control group was fed a standard diet, while the other groups were fed a high-fat diet to establish the NAFLD model. After successful modeling, the JPXZ-L, JPXZ-M, and JPXZ-H groups were administered JPXZ via gavage at respective doses for 28 consecutive days. Serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) were measured. Histopathological changes and lipid droplet deposition in the liver were observed by hematoxylin-eosin (HE) and Oil Red O staining. Intracellular lipid droplets, autophagosomes, and autolysosomes were examined by electron microscopy. The mRNA expression levels of Beclin1 and LC3B in liver tissues were detected by quantitative real-time polymerase chain reaction (qRT-PCR). Results: Compared with the normal control group, the model group exhibited significantly increased serum levels of ALT, AST, ALP, TG, TC, and LDL-C (P < 0.01), and a significantly decreased level of HDL-C (P < 0.001). HE staining revealed significant inflammatory cell infiltration in the model group, and Oil Red O staining showed a marked increase in intracellular lipid droplets. Electron microscopy confirmed lipid droplet accumulation and the presence of a small number of autolysosomes in hepatocytes. qRT-PCR analysis showed significant downregulation of Beclin1 and LC3B mRNA expression (P < 0.001). Compared with the model group, the PPC, JPXZ-M, and JPXZ-H groups showed significantly decreased levels of ALT, AST, TG, TC, and LDL-C (P < 0.05). HE staining indicated reduced inflammatory cell infiltration and fewer fatty vacuoles, while Oil Red O staining demonstrated decreased hepatic lipid droplet deposition; these improvements were more pronounced with increasing doses of JPXZ. Furthermore, qRT-PCR revealed significant upregulation of Beclin1 and LC3B mRNA expression (P < 0.05). Conclusion: Jianpi Xiaozhi Decoction may ameliorate hepatic steatosis in NAFLD mice by enhancing autophagy. |
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