Protective Effects of Celastrol on Diabetic Liver Injury via TLR4/MyD88/NF-κB Signaling Pathway in Type 2 Diabetic Rats

被引：83

作者：

Han, Li-ping

Li, Chun-jun

Sun, Bei

Xie, Yun

Guan, Yue

Ma, Ze-jun

Chen, Li-ming ^{[1
]}

机构：

[1] Tianjin Med Univ, Metab Dis Hosp, Collaborat Innovat Ctr Tianjin Med Epigenet 2011, Key Lab Hormone & Dev,Minist Hlth, Tianjin 300070, Peoples R China

来源：

JOURNAL OF DIABETES RESEARCH | 2016年 / 2016卷

基金：

中国国家自然科学基金;

关键词：

NF-KAPPA-B; NONALCOHOLIC STEATOHEPATITIS; RECEPTOR; 4; INFLAMMATION; EXPRESSION; APOPTOSIS; DISEASE; OBESITY; CELLS; TNF;

D O I：

10.1155/2016/2641248

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Immune and inflammatory pathways play a central role in the pathogenesis of diabetic liver injury. Celastrol is a potent immunosuppressive and anti-inflammatory agent. So far, there is no evidence regarding the mechanism of innate immune alterations of celastrol on diabetic liver injury in type 2 diabetic animal models. The present study was aimed at investigating protective effects of celastrol on the liver injury in diabetic rats and at elucidating the possible involved mechanisms. We analyzed the liver histopathological and biochemical changes and the expressions of TLR4 mediated signaling pathway. Compared to the normal control group, diabetic rats were found to have obvious steatohepatitis and proinflammatory cytokine activities were significantly upregulated. Celastrol-treated diabetic rats show reduced hepatic inflammation and macrophages infiltration. The expressions of TLR4, MyD88, NF-kappa B, and downstream inflammatory factors IL-1 beta and TNF alpha in the hepatic tissue of treated rats were downregulated in a dose-dependent manner. We firstly found that celastrol treatment could delay the progression of diabetic liver disease in type 2 diabetic rats via inhibition of TLR4/MyD88/NF-kappa B signaling cascade pathways and its downstream inflammatory effectors.

引用

页数：10

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