姜黄素衍生物L6H4对2型糖尿病大鼠肝组织的保护作用

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Abstract Objective: To investigate the protective effect and its mechanism of curcumin derivative L6H4 on hepatic tissue from type 2 diabetic and hyperlipidemic rats. Methods: Forty male Sprague-Dawley (SD) rats were randomly divided into five groups evenly, normal control group, high fat group, high fat+L6H4 treated group, diabetes mellitus group and diabetes mellitus+L6H4 treated group. The rats were fed with high fat and high sugar diet to induce hyperlipidemic model, and then injected with streptozotocin intraperitoneally to induce type 2 diabetic models. Rats in high fat+L6H4 treated group and diabetes mellitus+L6H4 treated group were given a gavage of curcumin derivative L6H4 at a dosage of 0.2 mg•kg-1•d-1 for 8 weeks. After the treatment, blood glucose and lipid levels as well as serum liver function indexes: alanine aminotransferase (ALT), aspartate aminotransferase (AST), albumin (ALB) were measured by automatic biochemical analyzer, free blood insulin (FIN) was tested by radioimmunoassay and homeostasis model assessment of insulin resistance (HOMA-IR) were calculated. The morphology of liver was observed under light microscope and transmission electron microscope. The expression of transforming growth factor β1 (TGF-β1), tissue inhibitor metalloprotemase 2 (TIMP-2) and matrix metalloproteinase 2 (MMP-2) were measured by immunohistochemical method. Results: Compared with normal control group, blood glucose and lipid levels, ALT as well as AST were significantly increased while ALB was significantly decreased in high fat and diabetes mellitus groups. After the treatment of L6H4, blood glucose and lipid levels as well as serum liver function indexes (ALT, AST) were markedly decreased while ALB was increased in high fat+L6H4 treated group and diabetes mellitus+L6H4 treated groups. Fatty degeneration and mild proliferation of fibrous tissue could be observed in high fat group, and the diabetes mellitus group showed further damage with focal necrosis, more pronounced fatty degeneration, and destruction of the hepatic cord, proliferation of fibrous tissue was remarkable, resulting in the thicker septa and the well observed deposition of collagen fiber in portal area, and were relived by the treatment of L6H4. The expression of TGF-β1, TIMP-2 and MMP-2 were markedly increased in high fat group and diabetes mellitus group, after the appliance of L6H4, TGF-β1 and TIMP-2 were decreased while MMP-2 was increased. Conclusion: Curcumin derivative L6H4 shows an effect in attenuating insulin resistance and regulating glucolipid metabolism, and exerts protective effect on the hepatic tissue from type 2 diabetic rats, down-regulation of the expression of TGF-β1, TIMP-2 and up-regulation of MMP-2 maybe involved in it.

Key words： diabetes mellitus curcumin derivative L6H4 hepatic fibrosis transforming growth factor β1 tissue inhibitor metalloprotemase 2 matrix metalloproteinase 2 rats

Received: 05 July 2017

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	DONG Xidan
	CHEN Xiaohu
	MIAO Chengfeng
	XU Feifei
	CHEN Sanmei
	CAI Guoping.

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https://xb.wmu.edu.cn/EN/ OR https://xb.wmu.edu.cn/EN/Y2017/V47/I12/888

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