| Rhodiola rosea is a precious plant, which is belonged to Rhodiola Sedum L. The main effective component of Rhodiola rosea is salidroside. Studies have been shown that the salidroside could improve immunity response, enhance physical performance, improve hematopoietic function and oxygen resistance of the human body. And it also has the function of anti-aging, anti-tumor, resist fatigue, blood sugar reduction, antivirus, radiation resistance, prevention of altitude sickness and others. Recent studies have shown that salidroside could not only reduce the level of blood sugar and improve glucose tolerance damage in type 2 diabetes, but also show promising treatment effect in type 2 diabetes patients complicated with cardiovascular disease, hyperlipidemia, renal disease and other complications.Several studies have found that mi RNA expression levels in adipocytes are significant different between normal and obese persons, especially in mature fat cells. Furthermore, a potential role for mi RNA in metabolic pathways have been suggested for glucose-stimulated insulin secretion from Pancreatic Islet cells. More evidences highlight the important role of mi RNA in the regulation of lipid metabolism in obesity of children. Accumulated evidences suggest that mi RNAs may be involved in diabetic glucose and lipid metabolism. Recently, several studies found that mi R-370 and mi R-122 are involved in the lipid metabolism, mi R-370 can directly regulate the rate-limiting enzyme of lipid β-oxidation, CPT-1. In addition, mi R-370 affects the biosynthesis and metabolism of lipid by regulating the expression level of mi R-122. Therefore, mi R-370 may be a drug target for diabetes treatment. However, few data are available for their role in diabetes. In my thesis, we investigated whether salidroside regulates glucose and lipid metabolism through mi R-370In the current study, we induced the type 2 diabetes model by feeding high-fat diet and intraperitoneal injecting STZ(100 mg, kg-1,) to male C56BL/6J mice. After 4 weeks, mice with fasting blood glucose levels above 7.8 mmol·L-1 were divided into five groups:Model group, Test groups treated with salidroside 40 mg·kg-1, 80 mg·kg-1, and 160 mg·kg-1 seperately, Metformin(480 mg·kg-1). After 4 weeks of treatment, fasting blood glucose, insulin sensitivity, oral glucose tolerance, blood lipid level and liver function indexes were measured. The results showed that compared with the control group mice, in the type 2 diabetic mice, the levels of fasting blood glucose, blood lipid and low density lipoprotein cholesterol(LDL-C) were significantly increased,while the level of high density lipoprotein cholesterol(HDL-C) decreased significantly. In addition,serum insulin levels were significantly lower, glucose tolerance was impaired, liver function was damaged, lipid was deposited in the liver, and mi R-370 levels were elevated in the serum and liver tissue. What’s more, expression of gluconeogenesis key protein(G6Pase and PEPCK) and lipid metabolism related proteins(SREBP-1c FAS, DGAT2) was significantly increased, and AMPK and CPT-1 protein expression were decreased. Interestingly, the abnormal expression pattern was reversed by the salidroside treatment. What’s more, the reverse effect had a certain dose dependent manner. We also tested the effect of salidroside by in vitro experiments. In mouse primary hepatocytes, we silenced or over-expressed mi R-370. Our results showed that compared with the normal control group, salidroside alone group and mir-370 inhibitor group were able to reduce the expression level of gluconeogenesis key protein(G6Pase and PEPCK) and lipid synthesis key protein(SREBP-1c, FAS-1, DGAT2), promote the expression of AMPK and CPT-1 protein expression. Mi R-370 mimic alone group can significantly increase hepatic gluconeogenesis by increasing the protein level of gluconeogenesis key protein(G6Pase and PEPCK), strengthen the lipid synthesis by increasing the protein level of its key protein(SREBP-1c, FAS-1, and DGAT2),and inhibit the AMPK and CPT-1 protein expression. Moreover, we found that compared with the mi R-370 mimic, combining mi R-370 mimic and salidroside can significantly reduce glucose and lipid metabolic disorder caused by mi R-370 mimic alone. The results showed that salidroside regulate the metabolism of glucose and lipid, at least in part, through the inhibition of mi R-370.In summary, our research found the treatment effects of salidroside on type 2 diabetic-caused blood glucose and lipid metabolic disorder, and for the first time proved that mi R-370 has an important role in the etiology of type 2 diabetes mellitus. We also found that salidroside can improve glucose and lipid metabolism disorder, at least in part, through the suppression of mi R-370 expression firstly. Our results provide a new insight into the the clinical application of salidroside for the treatment of type 2 diabetes. |
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