Study on Improvement Effect of Selenium-enriched Ganoderma lucidum Crude Extract on Lipid Metabolism ，Liver Function and Inflammatory Response in Type 2 Diabetic Model Rats and Its Mechanism / 中国药房

ABSTRACT

OBJECTIVE： To study the effects of selenium-enriched Ganoderma lucidum crude extract on lipid metabolism， liver function and inflammatory response in type 2 diabetic model rats. METHODS： Totally 120 rats were randomly divided into normal control group （n＝20， normal saline） and model group （n＝100）. Normal control group was fed with normal diet， and model group was fed with high-fat diet. 4 weeks later， model group was given intraperitoneal injection of Streptozotocin solution （30 mg/kg） to induce T2DM model. After modeling， 90 rats were randomly subdivided into model control group （normal saline）， positive control group （metformin， 200 mg/kg） and selenium-enriched G. lucidum crude extract low-dose， medium-dose and high-dose groups （300， 600， 1 200 mg/kg， calculated by extract）， with 18 rats in each group. They were given medicine intragastrically， once a day， from Monday to Saturday. Half of rats in each group were selected 4， 8 weeks after medication； the serum levels of glucose and insulin were detected， and islet resistance index were calculated. The serum levels of liver function indexes （AST， ALT， AKP）， blood lipid indexes （FFA， TC， TG， LDL-C） and inflammatory factors （TNF-α， IL-6， IL-1β） were detected by ELISA. After HE staining， the histopathological changes of liver tissue were observed by microscopy. mRNA and protein expressions of peroxisome proliferator activated receptor α （PPARα） and peroxidase acyl coenzyme A oxidase 1 （ACOX1） in liver tissue were detected by RT-qPCR and Western blot assay. RESULTS： Compared with normal control group， glucose， insulin serum levels and islet resistance index were significantly increased （P＜0.01）； serum liver function indexes， blood lipid indexes and inflammatory factor levels of model control group were increased significantly in model control group after 4 and 8 weeks medication （P＜0.05 or P＜0.01）. The hepatocyte swelling of model control group was round and the volume was significantly larger than that of blank control group.  The liver had different degrees of steatosis and vacuolization， accompanied by a small amount of inflammatory cell infiltration. mRNA and protein expressions of PPARα and ACOX1 in liver tissue were decreased significantly （P＜0.05 or P＜0.01）. Compared with model control group， except that there was no significant decreased in islet resistunce index and AST， ALT， IL-6， IL-1β serum levels after 4 weeks of medication， and glucose， insulin， ALT serum levels after 8 weeks of medication and the levels of 4 blood lipid indexes after 4 and 8 weeks of medication in selenium-enriched G. lucidum crude extract low-dose group （P＞0.05）， above serum indexes of other groups were decreased significantly after 4 and 8 weeks of medication （P＜0.05 or P＜0.01）. After 4 and 8 weeks of medication， the pathological changes of liver tissue in rats were alleviated in varying degrees. protein and mRNA expressions of PPARα and ACOX1 in liver tissue were increased significantly after 4 and 8 weeks of medication （P＜0.05 or P＜0.01）. CONCLUSIONS： Selenium-enriched G. lucidum crude extract can up-regulate protein and mRNA expressions of PPARα and ACOX1 in liver tissue， promote the excretion of accumulated fatty acid and significantly improve fatty acid metabolism， inflammatory response and liver function in T2DM model rats.