Prevention Effect And Active Mechanism Of Didangtang On Improving The Insulin Resistance Induced By High Fat Diet In Rats

Objective: Through high-fat diet induced insulin resistance model of rats, to observe the influence of Didangtang on insulin receptor, insulin-like growth factor-1 of aortic tissue, serum insulin growth factor-1, nitric oxide, endothelin, explore the mechanism of Didangtang on improving insulin sensitivity and provide theoretical basis for clinical application. Insulin play a role after combining with insulin receptor (InsR). If insulin receptor function become weak or reduced in quantity, which made insulin cannot play its proper role, insulin resistance would hanppen. Many of tissues of human body can secrete insulin-like growth factor-1, which has similar action of insulin, may improve insulin resistance, also has role of protecting coronary artery, while IR is of the important causes of endothelial impairation, which can worsen coronary artery disease.Didangtang is originated from ShangHanZaBingLun written by ZhangZhongJing in Dong Han Dynasiy, composed of rhubarb, peach kernel, Tabanus and leeches 4 herbs. It is a classical prescription to treat excessive pattern of stagnated blood with the effects of promoting blood circulation for removing obstruction in collaterals and eliminating blood stasis by catharsis. In this experiment, the method of high-fat feed was applied to copy insulin resistance model. Di dangtang was gave to theat it. The changes of the above indexes in IR rats were observed, to explore the mechanism of Didangtang on improving insulin resistance, and provide theoretical basis for better clinical application of Didangtang.Method:1 Experimental animals: 35 health and clean level Wistar male rats of weight for 200g±20g were chosen and randomly divided into 5 groups, respectively N = 7, the control group(Ⅰ), model group(Ⅱ), low-dose Di Dang Tang group(Ⅲ), high-dose Di Dang Tang group(Ⅳ), Xue Zhi Kang group(Ⅴ).2 The administion of drugs: the rats ofⅠgroup were fed with normal diet and distilled water (10ml/kg.d);Ⅱgroup was fed with high fat diet and distilled water (10ml/kg.d);Ⅲgroup was fed with high fat diet and 1g of Didingtang(crude drug/kg.d);Ⅳgroup was fed with high fat diet and 2g of Didingtang(crude drug/kg.d);Ⅴgroup was fed with high fat diet and 0.2 g/Kg.d of Xuezhikang.3 Indicators: After 8 weeks of feeding, take blood by decapitate, Serum FBG, INS, IGF-1, NO, ET were detected, HOMA-IR and ISI were Calculated, thoracic aorta was retained, Immunohistochemistry was used to observe the InsR, IGF-1 changes of aortic tissue.Results:1 Effect of Didangtang on IR insulin resistance index, insulin sensitivity indexThe results shows: compared with control group, HOMA-IR was increased, the level of ISI was Statistically reduced in rats of model group (P<0.01 or P<0.05), it shows that on a IR model of rats induced by high-fat diet was successful copied; compared with model group, HOMA-IR was significantly reduced in rats of low and high dose groups, ISI was significantly higher, with statistically significant difference (P<0.05 or P<0.01); low group compared with high groups, HOMA-IR of low group was lower, ISI was increased, that was a trendency that the effect in low dose group was better than that in high group, but without statistical significance(P>0.05); compared with Xuezhi Kang group, there were no statistical significance in low and high dose groups(P>0.05). which indicated that Didangtang can improveinsulin resistance, increase insulin sensitivity.2 Effect of Didangtang on aorta InsR of the IR rat The results shows: positive InsR expression was tan-yellow, comp- ared with control group, expression of the InsR on Smooth muscle cell membrane and cytoplasmic were weaker in model group, there was Statistically significant difference in average optical density(AOD) in this two groups(P<0.05), InsR expression can be reduced by IR; compared with model group, the InsR expression on Smooth muscle cell membrane and cytoplasmic were deeper in low-dose and high-dose Di Dang Tang groups, there was statistically significant difference in AOD(P<0.05). low group compared with high group, the InsR expression on Smooth muscle cell membrane and cytoplasmic were not obvious difference, there was no significant differences in AOD(P>0.05).compared with Xuezhikang group, the InsR exPression on Smooth muscle cell membrane and cytoplasmic were not obvious different in low and high groups, without significant differences in AOD(P>0.05). That InsR exPression on smooth muscle cell membrane and cytoplasm were increased by Didangtang. This may be one of the mechanisms of Didingtang on improving IR.3 Effect of Didangtang on IGF-1 of the IR ratsThe results shows: compared withⅠgroup, Rats serum IGF-1 content was decreased obviously in model group, with statistically significant difference(P<0.05), which indicates that serum IGF-1 was reduced when the IR occurs; compared with model group, Serum IGF-1 significantly increased in low and high groups, with statistically significant difference(P<0.05); compared with high-dose Di Dang Tang group, there was a increasing trendency in high-dose group than in low group, but there was not significant difference(P>0.05); low group, high group and Xuezhikang group were compared with each other, Increasing trendency of the former than the latter, but there was not significant difference(P>0.05); The serum IGF-1 can be increased by Didangtang, Which may be one of the mechanisms to improve the IR.4 Effect of Didangtang on aorta IGF-1 of the IR ratThe results shows: The Positive expression of IGF-1 was tan-yellow, comPared with control group, expression of the IGF-1 on smooth muscle cell membrane and cytoplasmic were weaker in model group, there was statistically significant difference in the average optical density (AOD) between the two groups (P<0.05), IGF-1 expression can be reduced by IR; compared with model group, the IGF-1 expression on Rats smooth muscle cell boundaries and cytoplasm were deepper in low and high-dose groups, statistically significant difference in AOD(P<0.05). compared with high group, the IGF-1 expression on Rats smooth muscle cell boundaries and cytoplasm were not obvious low group, there was no significant difference in AOD(P>0.05). compared with Xuezhikang group, IGF-1 expression on Rats smooth muscle cell boundaries and cytoplasm were not obvious difference in low and high-dose groups, without significant differences in AOD(P>0.05). The IGF-1 expression on smooth muscle cell membrane and cytoplasm can be increased by Didangtang. This may be one of the mechanisms of Didangtang on improving IR.5 effects Didangtang on serum ET, NO of IR ratsThe results shows: compared with control group, serum ET levels were increased, NO was decreased, with statistically significant difference in model group (P<0.05 or P<0.01), That endothelial damage can be induced by IR; comPared with model group, serum ET levels were decreased, NO content was increased, with statistically significant difference in low and high-dose groups (P<0.05 or P<0.01); there was no significant difference between low and high groups (P>0.05). and compared with Xuezhikang group, there were no significant difference in low and high-dose groups (P>0.05). which shows that the Endothelial function damaged by IR can be protected by Didangtang.Conclusions:1 Didangtang can reduce HOMA-IR, increase ISI, improve insulin sensitivity in the IR rats.2 Didangtang can improve the insulin receptor expression, improve insulin resistance in the IR rats. 3 Didangtang can increase the serum and aortic tissue IGF-1 levels, improve insulin resistance in IR rats4 Didangtang can imProve NO, reduce ET, protect the IR damaged endothelial function.