| Objective:To obverse the effects of Huayuwendan tang on ins-ulin resistance(IR) in high-fat diet fed Wistar rats,and to investigate the mechanism on protection of rat from insulin resistance in oxidat-ive injury.Methods:sixty-five Wistar rats (male,weight 150±30g) were es-tablished into insulin resistant models by feeding them with high fat diet, and then randomly divided into three groups:high-fat diet group, Huayuwendan tang group, metformin group. Besides, a normal group was set up for control. Administration of Huayuwendan tang or metformin lasted 4 weeks. During the experiment,the intraperitoneal glucosetolerance test (IPGTT) was performed at the 4th weeks. Blood glucose levels were determined at 0,60 and 120 min after glucose administration, and the areas under the glucose curves (AUC) were calculated. And the serum levels of insulin were also measured, and HOMA-IR were calculated. At the end of the experiment, the liver tissues were collected to test the index of oxidative stress, including the content of SOD,MDA,GSH and CAT.The blood was also collected to test IL-6,TNF-α.Serine phosphorylation of IRS1 (Ser307), IKKβ and NF-κB were tested in order to investigate insulin sensitivity wit-hin the liver.Results:1. Lee’s,TG,TC and FFA level:compared with high-fat diet group group,both Huayuwendan tang group and metformin group had a low-er level (p<0.05). Lee’s,TG,TC and FFA in Huayuwendan tang group and the metformin group were no significant difference(P>0.05).2. Intraperitoneal glucose tolerance and serum insulin levelrco-mpared with high-fat diet group,both Huayuwendan tang group and metformin group had a lower blood glucose level and smaller AUC of blood glucose(p<0.05).Both Huayuwendan group and metform group had a lower serum insulin(p<0.05) compared with high-fat diet group. In addition, the HOMA-IR of drug groups were lower than high-fat diet group(p< 0.05)3. Index of oxidative stress in liver tissue:compared with high-fat diet group, the level of SOD,GSH and CAT were higher(P<0.05) while the level of MDA were lower(P<0.05) in the Huayuwendan tang group and metformin group; compared with metformin group,SOD,GS H and CAT were no significant difference(P>0.05).4. Index of IL-6,TNF-α:compared with high-fat diet group, the level of IL-6 and TNF-α were lower (P<0.05) in the Huayuwendan tang group and metformin group; compared with metformin group,SO D,GSH and CAT were no significant difference(P>0.05).5. Insulin signaling pathway in the liver:compared with high-fat diet group, IRS1(Ser307), NF-κB and IKKβ phosphorylation were red uced (P<0.05),in both Huayuwendan tang group and metformin group. While there was no significantly difference in Huayuwendan tang gro up and metformin group.Conclusion:1. Huayuwendan tang could ameliorate glucose tolerance,decrea se serum insulin level and improve the insulin sensitivity of IR rats.2. Huayuwendan tang could reduce the level of IL-6 and TNF-α, and its function was better than metformin.3. Huayuwendan tang could improve the antioxidant capacity of liver, and its function was better than metformin.4. Huayuwendan tang could attenuate the insulin resistance in IR rats,its pharmaceutical mechanisms might be closely related with the reduction of phosphorylation levels of IRS1(Ser307), IKKβ and NF-KB,as well as the improvement of insulin signal transduction in liver tissue.5.Huayuwendan tang had protective effect on the high fat diet-induced IR rats probably because of reducing oxidative stress in liver tissue. |
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