Qilan Tangzhining Capsule Compound And Then Optimize The Two-tone And Its Glycolipid Mechanism

Diabetes Mellitus (DM) is a complex disease, not only relates to glycometabolism, but also to lipid metabolism disorder, and the lipid metabolism disorder is not totally secondary with glycometabolism. So just control the level of serum glucose can not eliminate the Complication and von Willebrand Factor in Type 2 Diabetic Patients completely, and we always treat it with regulate the lipid metabolism. The traditional Chinese multi-prescription focus on integral regulation of metabolism, and treat branch and root, so it present a large potential in treatment of diabetes mellitus with hyperlipemia.Qilan Tangzhining capsule have the effect of regulating both glycometabolism and lipid metabolism, consist of radix astragali, Gold Theragran, red rice, etc.The ingredients is complex, and take inconvenient of production and quality controlling. So we make this prescription as an object, further optimized it with direct experimental design, and then research the mechanism of regulating glycometabolism and lipid metabolism of the optimized prescription.1 literature research1.1 Insulin resistant and diabetes with hyperlipemia We have reviewed DM-related literature in the past 10 years home and abroad, interpreting that the insulin resistant is the common disease causes of glycometabolism and lipid metabolism disorder, and having a good hand of the present study of insulin resistant, DM and hyperlipoidemia.1.2 Study advancement of Further optimization of prescription(FOP) we have reviewed FOP-related literature, such as experiment design and data optimizing methods, mastered the research development of related project.2 Laboratory experiments2.1 further optimization of Qilan Tangzhining prescription Use the direct experimental design to arrange the animal experiment, obtain the information, and based on FOP theory and expertise, consider the interaction of drugs into variable screen, doing multiple linear regression analysis with SAS software, and obtain the regression equation correspond to different effect index, then predict the best optimized prescription. According to the frequency of ingredients and dosages in different optimized prescription, recombine the best prescription—Tangzhining capsule.The best prescription—Tangzhining capsule consist of Radix Astragalus, Radix Puerariae, and so on, according to traditional Chinese medicine theory and with excellent prescription ingredient, with indications of nourishing qi to invigorate the spleen, promoting the production of body fluid to quench thirst, and remove stasis and transform turbid.2.2 The best prescription's Efficacy Study Diabetic with Hyperlipoidemia model was induced by a high fat diet with intraperitoneal injection of streptozotic into male Wistar rats at a low dose. The effects of Qilan Tangzhining capsule on glycometabolism, lipid metabolism, and pathomorphological changes of liver and pancreas were observed among modeled rats.2.2.1Serum biochemics tests of glycometabolism After treatment for 6 weeks, the diformin group, the medium-dose and low-dose Tangzhining groups significantly lower down the blood-fasting sugar level of model rats, while the effect of disproof group is not as good as Tangzhining groups. Sugar tolerance test in rat indicated that the high dose, medium-dose and low-dose Tangzhining groups significantly lower down the area under the sugar tolerance curve, and do better than that of disproof groups.2.2.2 Serum biochemics tests of lipid metabolism After treatment for 6 weeks, serum level of cholesterol and triglyceride of model group are decreased, we think it relate to the ceasing of high fat diet and the rat ability of removing lipid.The result shows that Tangzhining groups of all doses have the significant effect of cutting down serum level of cholesterol, triglyceride, LDL-cholesterol, and elevating serum level of HDL-cholesterol.2.2.3 HE stain of pancreas and liver tissues of rats The result indicates that Tangzhining groups of all doses can improve pathological impairment of pancreas and liver. And the effects are better than that of disproof group.In general, Primary pharmacodynamics proves that FOP theory is scientific and feasible; Tangzhining capsule is well-formulated and effective in treating DM with hyperlipoidemia.2.3 Mechanism approaches2.3.1 The effect of before insulin receptor levelUse of radio-immunity method in studying the effects of Tangzhining capsule on serum insulin in experimental DM rats with hyperlipoidemia. The result shows that high-dose Tangzhining capsule significantly decreases the serum insulin level and improve the insulin sensitive. The medium-dose and low-dose Tangzhining capsule groups have no significant effect on serum insulin but can improve insulin sensitive significantly.Use of immunohistochemical method in studying the effects of Tangzhining capsule on pathomorphological changes of pancreaticβcells andαcells in experimental DM rats with hyperlipoidemia. The result shows that Tangzhining capsule increases the number of insulin positiveβcells and positive reactions while glucagons positiveαcells decrease in number and positive reactions are less compared with model group. It suggests that Tangzhining capsule can repair pancreaticβcell impairment, inhibit the secretion of glucagons fromαcells and lower down blood sugar level in DM rats with hyperlipoidemia.2.3.2 The effect of PI-3K signal conduction path (after insulin receptor level) Use of immunohistochemical method in studying the effects of Tangzhining capsule on IRS-2 and PI-3K expression of the liver. The result shows that Tangzhining capsule dosages groups improve the expression of IRS-2 compare with model group. The low-dose Tangzhining group improve the expression of PI-3K while the medium-dose and high-dose Tangzhining groups improve the expression of PI-3K with no significant deviation.Use of RT-PCR semiquantitive analysis in studying the effects of Tangzhining capsule on the expression of GluT4 mRNA of skeletal muscle on experimental DM rats with hyperlipoidemia. The result shows that low-dose and high-dose Tangzhining groups increase the expressions of GluT4 mRNA.The above result indicates that Qilan Tangzhining capsule may enhancing the expressions of IRS-2, PI-3K and GluT4 mRNA. Therefore, it can improve the insulin signal conduction from multi-site, and help the insulin play the normal role in regulating glycometabolism and lipid metabolism.2.3.3 The effect of PPARγand adipocytokinesUse of immunohistochemical method in studying the effects of Tangzhining capsule on PPARγexpression of the liver. The result shows that high-dose and medium-dose Tangzhining groups improve the expression of PPARγcompare with model group. PPARγnot only can regulate the lipid metabolism, but also can inhibit the release of TNF-αand FFA and regulate glycometabolism. So the result indicated that Tangzhining capsule can improve insulin sensitive by activating the PPARγ.Use of ELISA method in studying the effects of Tangzhining capsule on tumor mecrosis factor (TNF-α) expression in adipocyte. The result shows that the TNF-αdensity in high-dose and medium-dose are significently lower down than that of model group. It indicate that Tangzhining capsule can improve insulin sensitive by low down the level of TNF-α, and then remove the inhibition of the GluT4 in adepocyte and skeletal, and stimulate the lipoclasis.Use of chromatometry method in studying the effects of Tangzhining capsule on serum FFA level. The result shows that Tangzhining capsule dosages groups have the effect of lowing down the serum FFA level. Tangzhining capsule can regulate glycometabolism and lipid metabolism by cutting down the impairment of FFA.In a word, the further optimization prescription theory is scientific and feasibility. And the best prescription which screened have the effect of decreasing the blood sugar level and lipid level. And the optimized prescription regulate glycometabolism and lipid metabolism with affecting of the insulin signal conduction by the multi-angle and multi-target.