茵陈芍甘汤对内毒素性急性肝损伤小鼠NLRP3炎症小体的影响

Effect of Yinchen Shaogan Decoction on NLRP3 Inflammasome of Endotoxin- induced Acute Liver Injury's Mice

目的:观察茵陈芍甘汤对内毒素性急性肝损伤的影响及对NLRP3炎症小体表达的影响。方法:取健康雄性ICR小鼠50只,按数字表法随机分为正常组、模型组、水飞蓟素组、茵陈芍甘汤高剂量组及茵陈芍甘汤低剂量组。各组第一次给药干预1 h后,除正常组腹腔注射生理盐水1 m L外,其余各组均以10μg/kg LPS+600mg/kg D-Gal N用1 m L生理盐水溶解后腹腔注射造成急性肝损伤模型。观察造模并药物干预后各组小鼠肝脏病理组织改变,检测血清丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST)、IL-1β水平及肝脏组织Cryopyrin、Caspase-1蛋白表达。结果:与正常组比较,造模后小鼠肝脏组织炎症明显,肝细胞水肿、坏死。血清IL-1β含量明显上升(P<0.01),肝组织Caspase-1、Cryopyrin蛋白的表达水平显著升高(P<0.05或P<0.01),但ALT和AST水平变化不明显(P>0.05)。与模型组比较,茵陈芍甘汤治疗组肝细胞肿胀及空泡样变性减轻,肝细胞呈少量点状坏死,炎症细胞浸润减少。血清IL-1β含量明显下降(P<0.05),肝组织Caspase-1、Cryopyrin蛋白的表达水平明显降低(P<0.05或P<0.01),ALT和AST水平变化不明显(P>0.05)。结论:茵陈芍甘汤对内毒性急性肝损伤小鼠有明显的保护作用,其机制可能与其降低了急性肝损伤小鼠血清IL-1β以及肝组织Caspase-1、Cryopyrin蛋白的表达水平有关。

Objective： To study the impact of Yinchen Shaogan Decoction on NLRP3 inflammasome of endotoxin- induced acute liver injury ＇s mice. Methods： Fifty healthy male mice were randomly divided into five groups（ the control group,the model group,the silymarin group,the high dose of Yinchen Shaogan Decoction group and the low dose of Yinchen Shaogan Decoction group）. After an hour of drug intervention for the first gavage,in addition the control group received intraperitoneal injections of 1 m L normal saline,the other groups received intraperitoneal injections of LPS（ 10μg /kg） and D- Ga LN（ 600 mg /kg） in 1 m L stroke- physiological saline solution to induce the model of acute liver injury. The HE staining for liver tissues were performed and serum ALT,AST,IL- 1β and Caspase- 1 and Cryopyrin protein were also examined. Results： Compared with the normal liver tissue,the pathological changes in acute liver injury＇s mice had inflammation and the hepatocyte edema and necrosis. The expressions of IL- 1β and Caspase- 1,Cryopyrin protein were significantly increased（ P 〈0. 01 or P 〈0. 05） compared with that of the control group. However,the expressions of ALT and AST were not changed significantly（ P 〉0. 05）. Campared with that of the model group,the high or low doses of Yinchen Shaogan Decoction groups ＇ hepatocyte edema,cellular vacuolar degeneration and infiltration of inflammatory cells were significantly reduced and the hepatocyte had only a small spot necrosis. The expressions of IL- 1βand Caspase- 1,Cryopyrin protein were significantly reduced（ P 〈0. 01 or P 〈0. 05）,but the changes of the expressions of ALT and AST were not significant（ P 〉0. 05）. Conclusion： Yinchen Shaogan Decoction has significantly protective impact on endotoxin- induced acute liver injury＇s mice and its underlying mechanism could be reducing the expressions of serum IL- 1β and the live tissue Caspase- 1 and Cryopyrin protein.