探讨柴胡桂枝干姜汤对非酒精性脂肪肝（NAFLD）大鼠的治疗作用及机制。【方法】实验设正常组，模型组，中 药（柴胡桂枝干姜汤）低、高剂量组及GSK872[受体相互作用蛋白激酶（RIP）3抑制剂]组等5组。除正常组，其余各组大鼠分别 采用高脂饲料饲喂法构建NAFLD模型。治疗结束后，采用原位末端转移酶标记（TUNEL）法观察肝细胞凋亡情况，酶联免疫 吸附分析（ELISA）检测中血清中谷丙转氨酶（ALT）、谷草转氨酶（AST），血脂[总胆固醇（TC）、甘油三酯（TG）、低密度脂蛋白 胆固醇（LDL-C）、高密度脂蛋白胆固醇（HDL-C）]水平及肝组织中炎症因子肿瘤坏死因子α（TNF-α）、白细胞介素1β（IL-1β） 水平，Western Blot法检测肝组织中RIP1、RIP3、混合谱系激酶结构域样蛋白（MLKL）磷酸化水平。【结果】与正常组比较， 模型组大鼠肝细胞凋亡指数升高，血清中ALT、AST及TC、TG、LDL-C水平显著升高，HDL-C水平显著降低，肝组织中 TNF-α、IL-1β含量及RIP1、RIP3、MLKL磷酸化表达水平均显著升高（P＜0.05）；与模型组比较，中药低、高剂量组及 GSK872组大鼠肝细胞凋亡指数降低，血清中ALT、AST及TC、TG、LDL-C水平显著降低，HDL-C水平显著升高，肝组织 中TNF-α、IL-1β 含量及RIP1、RIP3、MLKL 磷酸化表达水平均显著降低（P＜0.05）；中药低、高剂量组上述各指标与 GSK872组比较，差异均无统计学意义（P＞0.05）。【结论】柴胡桂枝干姜汤可以有效改善大鼠NAFLD，其机制可能与抑制 RIP1/RIP3/MLKL信号通路活化，进而抑制坏死性凋亡有关。

To investigate the therapeutic effect and mechanism of Chaihu Guizhi Ganjiang Decoction on non-alcoholic fatty liver disease（NAFLD）rats. Methods The experiment was conducted in five groups：normal group，model group，low- and high- dose groups of Chinese medicine（Chaihu Guizhi Ganjiang Decoction）and GSK872 [receptor interacting protein kinase（RIP）3 inhibitor] group. Except for the normal group，the NAFLD rat model was constructed using high-fat chow feeding method in the remaining groups，respectively. At the end of treatment，hepatocyte apoptosis was observed by terminal transferase uridyl nick end labeling（TUNEL）method， and serum levels of alanine aminotransferase（ALT），aspartate aminotransferase（AST），lipids [total cholesterol （TC），triglycerides（TG），low-density lipoprotein cholesterol（LDL-C），high-density lipoprotein cholesterol （HDL-C）]，and the levels of inflammatory factors tumor necrosis factor α（TNF-α）and interleukin 1β（IL-1β）in liver tissues were measured by enzyme-linked immunosorbent assay（ELISA）；and the levels of phosphorylation of RIP1，RIP3，and mixed lineage kinase structural domain-like protein（MLKL）were detected in liver tissues by Western Blot. Results Compared with the normal group，the apoptotic index of rat hepatocytes in the model group was elevated，ALT and AST in serum were significantly elevated，TC，TG and LDL-C levels were significantly elevated， and HDL-C level was significantly reduced， and the contents of TNF-α and IL-1β as well as the phosphorylated expression levels of RIP1， RIP3 and MLKL were significantly elevated in the liver tissues（P＜ 0.05）； compared with the model group， the apoptotic index of hepatocytes in rats in the low- and high- dose groups of Chinese medicine and GSK872 group was reduced，the serum levels of ALT and AST were significantly reduced， the levels of TC， TG and LDL-C were significantly reduced， the level of HDL-C was significantly increased，and the contents of TNF-α and IL-1β and the phosphorylated expressions of RIP1，RIP3 and MLKL in the liver tissues were significantly reduced（P＜0.05）； there was no significant difference in the abovementioned indexes between the low-dose and high-dose groups of Chinese medicine and the GSK872 group（P＞ 0.05）. Conclusion Chaihu Guizhi Ganjiang Decoction can effectively improve NAFLD in rats，and its mechanism may be related to the inhibition of RIP1/RIP3/MLKL signaling pathway activation，which in turn inhibits necrotic apoptosis.

R285.5

湖北省中医药科研立项项目（编号：ZY2023F036）