厄贝沙坦通过诱导自噬减轻db/db小鼠肝脏脂肪变

Irbesartan alleviates hepatic steatosis in db/db mice by inducing autophagy

目的:探讨厄贝沙坦对db/db小鼠脂肪肝的影响及自噬在这一过程中的作用。方法:雄性db/db小鼠24只随机分为模型组和厄贝沙坦组,另选取12只db/m小鼠作为正常对照组。各组分别干预16周后,观察体重、肝指数、血脂、肝功能以及肝脏病理的变化,检测肝组织PI3K/Akt/m TOR信号通路及自噬相关蛋白Atg-7、beclin-1和LC3B的表达情况,并利用电镜观察肝脏自噬小体的变化。结果:与模型组相比,应用厄贝沙坦干预后,db/db小鼠的体重、肝指数、血脂、丙氨酸转氨酶和天冬氨酸转氨酶与模型组相比显著降低(P<0.05),肝脏病理改变明显减轻;肝组织p-PI3K、p-Akt和p-m TOR的表达明显减少,Atg-7、beclin-1和LC3B-Ⅱ的表达明显增加,肝脏自噬小体显著增多(P<0.05)。结论:厄贝沙坦可能通过抑制PI3K/Akt/m TOR信号通路,上调自噬相关蛋白Atg-7、beclin-1和LC3B-Ⅱ表达,进而促进肝细胞自噬,减轻db/db小鼠肝脏脂肪变。

AIM:To investigate the effect of irbesartan on the fatty liver of db/db mice and whether autophagy is involved in the process.METHODS:Male db/db mice(n=24)were randomly divided into model group and irbesartan group,and12db/m mice with similar age and weight were selected as normal control group.After16weeks of intervention respectively,the fatty liver-related parameters including body weight,liver index,blood lipid,liver function and pathological changes in the liver were observed.The protein levels of p-PI3K,p-Akt,and p-mTOR,as well as Atg-7,beclin-1and LC3B in the liver tissues were detected by Western blot,and the autophagosomes in the liver were observed under electron microscope.RESULTS:Compared with the model group,the body weight,liver index,blood lipids,alanine and aspartate aminotransferase were decreased in irbesartan group(P<0.05).Moreover,the pathological changes in the liver were significantly ameliorated in irbesartan group than that of model group.Importantly,the protein levels of p-PI3K,p-Akt and p-mTOR were decreased with irbesartan administration,while the expression of Atg-7,beclin-1and LC3B-Ⅱwas increased(P<0.05),which resulted in a distinct increase in autophagosomes.CONCLUSION:Irbesartan alleviates hepatic steatosis in db/db mice by inhibiting the PI3K/Akt/mTOR signaling pathway and upregulating the protein expression of Atg-7,beclin-1and LC3B-Ⅱ,thereby inducing autophagy in hepatocytes.