| ObjectiveOn the basis of ancient literature, combined with today's clinical peculiarity of diabetes and complications of diabetes,probe into diabetes gastroparesis treatment for theoretical approach, and enrich Chinese medicine on diabetes stomach; Study the role of diabetes gastroparesis (DGP) rats gastric antral SCF-Kit pathway in the damage of interstitial cells of cajal (ICC) and the mechanism of TangWeiKang in order to lay the foundation to develop an effective medicine to control DGP.MethodsTheoretical studies:Research the origin, the pathogenesis and treatment methods of gastric disease of diabetes, and discuss TangWeikang's prescription principles and efficacy analysis.Experimental studies:At first,we have used Streptozotocin by cavitas abdominalis injection and high sugar high fat diet to irregularly feed (morning meal in odd-number days, afternoon eating in even-number days) rats to induce DGP model, and have divided rats into 7 Groups (normal comparison group, diabetes model group, diabetes gastroparesis model group,TangWeiKang high dose group, TangWeiKang medium dose group, TangWeiKang low dose group and XiShaBiLi treatment group) for experimental research. Then we have observed TangWeiKang'influence on improving carbohydrate and lipid metabolism and pancreaticβcell function of DGP model group rats; and observed each group of rats gastric antrum ICC ultrastructure through transmission electron microscopy; and taken the Western blot to detect gastric tissue c-kit and SCF protein expression level, and taken RT-PCR to determinate the expression of gastric tissue SCF mRNA.Results.1.Gastric disease of diabetes has a pathogenesis characteristic that Ben is deficient and Biao is excess. Furthermore, the spleen's deficiency is the most important,and the toxic'exuberance is the most obvious. Aiming at these, we have established a prescription TangWeiKang that can make the spleen-stomach healthy and smooth Qi and eliminate toxins.2. In the research of making DM model and DGP model:Former 4 weeks after the model, quantities of food-intake of DM model group and DGP model group rats have obviously increased, compared with normal comparison group, and differences are significant (P<0.05 or P<0.01).Moreover, DM model group is more obvious. After 6 weeks, quantities of food-intake of DGP model group rats have decreased, compared with normal comparison group, and differences are significant in 8thweek(P<0.01). Former 2 weeks after the model, quantities of hydroposia of DM model group and DGP model group rats have obviously increased, compared with normal comparison group, and differences are significant (P<0.01). After 4 weeks, quantities of hydroposia of DGP model group rats have decreased more than that of DM model group.Besides, differences are more significant after 6 weeks, and are significant (P<0.05 or P<0.01). As an extension of time, the weights of DM model group and DGP model group rats have obviously reduced, compared with normal comparison group, and differences are signif icant(P<0.05 or P<0.01). Moreover, DGP model group is more obvious. and differences are significant (P<0.05 or P<0.01), compared with DM model group. At the same time, the stool of DM model group and DGP model group rats has appeared some changes, such as less, pale, softer, mutual adhesion, irregular shape and so on. Moreover, DGP model group is more obvious. The function of gastric emptying of DM model group and DGP model group rats has decreased, and the decline of gastric emptying of DM model group rats is non-obvious(P>0.05), compared with normal comparison group,but that of DGP model group rats is significant (P<0.01).3. TangWeiKang' influence on improving carbohydrate and lipid metabolism and pancreaticβcell function of DGP model group rats: Fasting plasma glucose and fasting serum insulin and Homa-IR of TangWeiKang high dose group and medium dose group rats have obviously descended,but insulin sensitivity index of TangWeiKang high dose group and medium dose group rats have went up. Islet cell shape of TangWeiKang high dose group and medium dose group rats is more regular, and quantity of cell is more,and endochylema is more rich, compared with DGP model group rats. But the function of gastric emptying of TangWeiKang high dose group and medium dose group rats has no obvious difference with XiShaBiLi treatment group rats. These have explained TangWeiKang high dose and medium dose can improve IR by means of reducing glucose, and raise insulin sensibility,and renew pancreaticβcell function, and relieve clinical symptoms. There are obvious lipid accumulation in langerhans'islet in the DM model group and DGP model group rats, which can be important pathology factors that come into being DM and DGP. The weights of model group (DM model group and DGP model group)rats have dropped obviously in the experiment later stage, and DGP model group is most obvious. The reason can be high plasma glucose that lead to fat to resolve. The weights of TangWeiKang high dose group and medium dose group rats have obviously increased after invasion, and the ratio of fat in viscera and weight has obviously decreased,which have illustrated TangWeiKang can adjust lipid and put off the progress of DM.4. TangWeiKang' influence on ICC of DGP model group rats:The gap joints between gastric antral ICC and smooth muscle and nerve endings have markedly decreased in the DGP model group rats through transmission electron microscopy, and the structures of intercellular connections are vague,and the gap has magnified. A part of ICC' basement layer has been separated with cytomembrane, which has formed cavity.we can also find mitochondria swelling, vacuolar degeneration,even dissolution, and cytoplasm resolving, and the quantity of cell organ has decreased. The gap joints between gastric antral ICC and smooth muscle and nerve endings are markedly more in the TangWeiKang high dose group and medium dose group than DGP model group after invasion, with more developed slide endoplasmic reticulum, Golgi apparatus and mitochondria. We have found the expression levels of c-kit protein of DGP model group have obviously decreased by western blot analysis method, compared with normal comparison group, and differences are significant (P<0.01). The expression levels of c-kit protein in the TangWeiKang high dose group and medium dose group are obviously higher than DGP model group after invasion (P<0.01), but the differences are non-obvious (P>0.05), compared with normal comparison group.5. TangWeiKang'influence on SCF protein and gene expression of DGP model group rats:We have found the expression levels of SCF protein and gene expression of DGP model group have obviously decreased, compared with normal comparison group, and differences are significant (P<0.01). The expression levels of SCF protein and gene expression in the TangWeiKang high dose group and medium dose group are obviously higher than DGP model group after invasion (P<0.05 or P<0.01), but the differences are non-obvious (P>0.05), compared with normal comparison group.Conclusion1. Spleen-deficiency and losing in the transformation and transportation is a key link during diabetes mellitus formation. Toxins, such as toxic heat, damp toxin, ecchymosis toxin, turbid toxin and so on, are not only pathological products of diabetes mellitus,but also important pathogenic factors during gastric disease of diabetes formation. Gastric disease of diabetes have a pathogenesis characteristic that Ben is deficient and Biao is excess. Furthermore, the spleen's deficiency is the most importance, and the toxic'exuberance is the most obvious. Treatment principle should combine Bing with Zheng,and treat Biao and Ben at the same time. Aiming at these, we have established a prescription TangWeiKang that can make the spleen-stomach healthy and smooth Qi and eliminate toxins.2. On the basis of single intraperitoneal injection STZ, we have fed model group rats on high sugar and high fat diet irregularly (morning meal in odd-number days, afternoon eating in even-number days).we have successfully copied diabetic gastroparesis model in this way.3.TangWeiKang have a positive influence on improving carbohydrate and lipid metabolism and pancreaticβcell function, to a certain extent, can improve the IR, restore pancreatic isletβcell functions, enhance gastric emptying of DGP, and these are at the dose-effect relationship. TangWeiKang may rebuild the SCF-Kit pathway for ICC phenotype reversion by upregulating the level of SCF, so as to maintain normal gastrointestinal motor function. |
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