| Objective: Diabetic gastropathy (DG) and diabetic nephropathy (DN) were the most common chronic complications of diabetic melliutus (DM), the two are often concurrent clinical. The symptom complex of DG typically associated with low motility of stomach. Diabetic gastroparesis is characterized by delayed gastric emptying and carries significant risk of morbidity and even mortality to the patient. Gastroparesis seriously affects the quality of life. Then it is important to study the pathogenesis of DG and look for effective methods to prevent and treat DG. DG was resulted from synthetic action of multiple factors with characteristics of complicated pathological mechanism. Scholars both at home and abroad continue to explore pathological mechanism and effective treatment. However until now, the pathogenesis is not clear yet. Favorable treatment and medicines are less. To treat DG in modern medicine, the important methods were to control high blood glucose (BG), control hypertension, maintain low-protein diet, correct the disorder of lipid metabolism and take gastrointestinal motility drugs. But the clinical effects were low with more adverse long-term application. Treatment of DG by traditional Chinese medicine (TCM) is typified with a multitude of ways, multi-target low adverse reactions. In recent years, good effect with TCM was acquired to cure DM, DG and DN, showing greater potential and potential applications. In clinical practice early, basic pathogenesis of DG was summarized by professor Chen Zhiqiang as'qi and yin deficiency, disease product obstructing the collaterals', according to TCM pathology'long illness will be virtual, long illness will lead to stasis', DM clinical manifestation, pathology and pathogenesis of DG and DN. Benefiting vital energy, nourishing yin, removing disease and flow of qi were the main therapy methods. Referring to experience of clinical medicine, prescription was a traditional chinese medicine compound containing astragalus, salvia, turtle shell and lumbricus with features of'benefiting vital energy, nourishing yin, removing disease and flow of qi'. The prescription showed good effect to cure DG and DN. Then the study was designed to verify the therapeutic effect and probe into the possible mechanism. This maybe also provide experimental evidence for'the same treatment for the different disease'. The prescription was used to treat DG animal model of gastric motility disorders observing the therapeutic effect, and testing gastrin, leptin and glucagon in serum, the expression of leptin and leptin receptor in stomach, stomach superoxide dismutase (SOD) and malondialdehyde (MDA). The influence of this prescription in gastric interstitial cells of cajal and SCF/c-kit signaling pathway was detected. It was designed to probe into the possible mechanism and to provide experimental evidence for clinical application.Methods:1 The effect and mechanism of Supplement Qi and Nourish Yin Resolve Masses and Dredge Meridians on gastric emptying of DN's rats.80 SD male rats were randomly divided into 5 groups: control group, model group, low dose treated group, middle dose treated group and high dose treated group. After 1 week adaptable feed, rats were tested urine protein negative and removed left kidney. After 2 weeks, others groups except for control were injected streptozotocin (STZ) solution (40mg/kg) into abdominal cavities. 72h later, blood glucose (BG)≥16.7 mmol/L were taken as the standard model. After 3 weeks, 24h protein quantitativeurine≥30mg demonstrated the success of DN rat model. The rats in low dose treated group, middle dose treated group and high dose treated group were given by intragastric administration with the Herbs of Supplement Qi and Nourish Yin Resolve Masses and Dredge Meridians respectively (5.29g/Kg.d, 10.58g/Kg.d, 21.16g/Kg.d) one time per day for 6 weeks. The rats in control group and model group were given by intragastric administration with the saline water. After 6 weeks, 24-hour urine was collected, and blood was sacrificed. BG, blood urea nitrogen (BUN), creatinine (Cr), Alanine transaminase (ALT), cholesterol and triglyceride (TG) were detected. After cardia and pylorus ligation, phenol red was administered to test gastric emptying function (GEF).2 The effect of Supplement Qi and Nourish Yin Resolve Masses and Dredge Meridians on gastrointestinal hormones in gastro-motor disorders (GMD) of DN's rats.2.1 The effect of Supplement Qi and Nourish Yin Resolve Masses and Dredge Meridians on serum leptin, stomach leptin and leptin receptor OB-Rb in GMD of DN's rats.2.1.1 The effect of Supplement Qi and Nourish Yin Resolve Masses and Dredge Meridians on serum leptin in GMD of DN's rats.DN GMD rat model was reconstructed ibid method. After 6 weeks with intragastric administration with the Herbs of Supplement Qi and Nourish Yin Resolve Masses and Dredge Meridians, blood and stomach were collected. Serum leptin were detected.2.1.2 The effect of Supplement Qi and Nourish Yin Resolve Masses and Dredge Meridians on stomach leptin in GMD of DN's rats.DN GMD rat model was reconstructed ibid method. After 6 weeks with intragastric administration with the Herbs of Supplement Qi and Nourish Yin Resolve Masses and Dredge Meridians, blood and stomach were collected. Stomach leptin were detected.2.1.3 The effect of Supplement Qi and Nourish Yin Resolve Masses and Dredge Meridians on Leptin receptor of stomach OB-Rb in GMD of DN's rats.DN GMD rat model was reconstructed ibid method. After 6 weeks with intragastric administration with the Herbs of Supplement Qi and Nourish Yin Resolve Masses and Dredge Meridians, blood and stomach were collected. Leptin receptor of stomach OB-Rb were detected.2.2 The effect of Supplement Qi and Nourish Yin Resolve Masses and Dredge Meridians on serum gastrin in GMD of DN's rats. DN GMD rat model was reconstructed ibid method. After 6 weeks with intragastric administration with the Herbs of Supplement Qi and Nourish Yin Resolve Masses and Dredge Meridians, blood was collected. Serum gastrin were detected.2.3 The effect of Supplement Qi and Nourish Yin Resolve Masses and Dredge Meridians on serum glucagon in GMD of DN's rats.DN GMD rat model was reconstructed ibid method. After 6 weeks with intragastric administration with the Herbs of Supplement Qi and Nourish Yin Resolve Masses and Dredge Meridians, blood was collected. Serum glucagon were detected.3 The effect of Supplement Qi and Nourish Yin Resolve Masses and Dredge Meridians on stomach SOD and MDA in diabetic GMD of DN's rats.DN GMD rat model was reconstructed ibid method. After 6 weeks with intragastric administration with the Herbs of Supplement Qi and Nourish Yin Resolve Masses and Dredge Meridians, stomach was collected. Stomach SOD and MDA were detected.5 The effect of Supplement Qi and Nourish Yin Resolve Masses and Dredge Meridians on ultrastructure of gastric cajal interstitial cells in diabetic GMD of DN's rats.DN GMD rat model was reconstructed ibid method. After 6 weeks with intragastric administration with the Herbs of Supplement Qi and Nourish Yin Resolve Masses and Dredge Meridians, stomach was collected. Ultrastructure of gastric cajal interstitial cells was observed.6 The effect of Supplement Qi and Nourish Yin Resolve Masses and Dredge Meridians on SCF/c-kit signaling pathway in diabetic GMD of DN's rats.DN GMD rat model was reconstructed ibid method. After 6 weeks with intragastric administration with the Herbs of Supplement Qi and Nourish Yin Resolve Masses and Dredge Meridians, stomach was collected. SCF and c-kit mRNA was detected.Results:1 The therapeutic effect of Supplement Qi and Nourish Yin Resolve Masses and Dredge Meridians on gastric emptying of DN.1.1 The comparison of gastric emptying rates (GERS) among 5 group ratsThe GERS were lower in model group, middle dose treated group and high dose treated group than those in control group (P<0.05). But there was no significant difference between low dose treated group and control group (P>0.05). The GERS were higher in low dose treated group, middle dose treated group and high dose treated group than those in model group (P<0.05). There were no significant difference among treated groups (P>0.05).1.2 The comparison of serum BUN among 5 group ratsSerum BUN was higher in model group than those in control group (P<0.01). Serum BUN were also higher in low dose treated group, middle dose treated group and high dose treated group than those in control group (P<0.05). Serum BUN were lower in low dose treated group, middle dose treated group and high dose treated group than those in model group (P<0.05). There were no significant difference among treated groups (P>0.05).1.3 The comparison of serum Cr among 5 group ratsSerum Cr was higher in model group than those in control group (P<0.05). But there was no significant difference among low dose treated group, middle dose treated group, high dose treated group and control group (P>0.05). Serum Cr were lower in low dose treated group, middle dose treated group and high dose treated group than those in model group (P<0.05).1.4 The comparison of serum TC among 5 group ratsSerum TC was higher in model group than those in control group (P<0.01). Serum TC were also higher in low dose treated group, middle dose treated group and high dose treated group than those in control group (P<0.05). Serum TC were lower in low dose treated group, middle dose treated group and high dose treated group than those in model group (P<0.05). There were no significant difference among treated groups (P>0.05).1.5 The comparison of serum TG among 5 group ratsSerum TG was higher in model group than those in control group (P<0.01). Serum TG were also higher in low dose treated group, middle dose treated group and high dose treated group than those in control group (P<0.05). Serum TG were lower in low dose treated group, middle dose treated group and high dose treated group than those in model group (P<0.05). There were no significant difference among treated groups (P>0.05).1.6 The comparison of BG among 5 group ratsBG was higher in model group than those in control group (P<0.01). BG were also higher in low dose treated group, middle dose treated group and high dose treated group than those in control group (P<0.01). BG were lower in low dose treated group, middle dose treated group and high dose treated group than those in model group (P<0.01). BG was lower in low dose treated group than those in middle dose treated group and high dose treated group (P<0.05).1.7 The comparison of serum ALT among 5 group ratsSerum ALT was higher in model group than those in control group (P<0.01). Serum ALT were also higher in low dose treated group, middle dose treated group and high dose treated group than those in control group (P<0.05). Serum ALT were lower in low dose treated group, middle dose treated group and high dose treated group than those in model group (P<0.05). There were no significant difference among treated groups (P>0.05).2 The effect of Supplement Qi and Nourish Yin Resolve Masses and Dredge Meridians on gastrointestinal hormones in GMD of DN's rats.2.1 The effect of Supplement Qi and Nourish Yin Resolve Masses and Dredge Meridians on serum leptin, stomach leptin and leptin receptor OB-Rb in GMD of DN rats.2.1.1 The level of serum leptin among 5 group ratsSerum leptin was higher in model group than those in control group (P<0.05). Serum leptin were higher in middle dose treated group and high dose treated group than those in control group (P<0.05). But there was no significant difference between low dose treated group and control group (P>0.05). Serum leptin were lower in low dose treated group, middle dose treated group and high dose treated group than those in model group (P<0.05). There were no significant difference between treated groups (P>0.05).2.1.2 The expression of stomach leptin among 5 group ratsStomach leptin was lower in model group than those in control group (P<0.01). Serum leptin were lower in low dose treated group, middle dose treated group and high dose treated group than those in control group (P<0.05). Stomach leptin were higher in low dose treated group, middle dose treated group and high dose treated group than those in model group (P<0.05). There were no significant difference between treated groups (P>0.05).2.1.3 The expression of stomach OB-Rb among 5 group ratsStomach OB-Rb was higher in model group than those in control group (P<0.01). Stomach OB-Rb were higher in low dose treated group, middle dose treated group and high dose treated group than those in control group (P<0.01). There were no significant difference between model group and treated groups (P>0.05).2.2 The effect of Supplement Qi and Nourish Yin Resolve Masses and Dredge Meridians on serum gastrin in GMD of DN rats.Serum gastrin was higher in model group than those in control group (P<0.05). But there were no significant difference between low dose treated group, middle dose treated group, high dose treated group and control group (P>0.05). Serum gastrin were lower in low dose treated group, middle dose treated group and high dose treated group than those in model group (P<0.05). There were no significant difference between treated groups (P>0.05).2.3 The effect of Supplement Qi and Nourish Yin Resolve Masses and Dredge Meridians on serum glucagon in GMD of DN rats.Serum glucagon was higher in model group than those in control group (P<0.05). But there were no significant difference between low dose treated group, middle dose treated group and control group (P>0.05). Serum glucagon were lower in low dose treated group, middle dose treated group and high dose treated group than those in model group (P<0.05). There were no significant difference between treated groups (P>0.05).3 The effect of Supplement Qi and Nourish Yin Resolve Masses and Dredge Meridians on stomach SOD and MDA in GMD of DN rats.3.1 The content of stomach MDA among 5 group ratsThe content of stomach MDA was higher in model group than those in control group (P<0.05). The content of stomach MDA were higher in low dose treated group, middle dose treated group and high dose treated group than those in control group (P<0.05). The content of stomach MDA were lower in low dose treated group, middle dose treated group and high dose treated group than those in model group (P<0.05).3.2 The activity of stomach SOD among 5 group ratsThe activity of stomach SOD was lower in model group than those in control group (P<0.05). The activity of stomach SOD were lower in low dose treated group, middle dose treated group and high dose treated group than those in control group (P<0.05). The activity of stomach SOD were higher in low dose treated group, middle dose treated group and high dose treated group than those in model group (P<0.05).4 The effect of Supplement Qi and Nourish Yin Resolve Masses and Dredge Meridians on ultrastructure of gastric cajal interstitial cells in GMD of DN rats.4.1 Light microscope observationsRats in control group had integrited gastric mucosa, lined glands, hypervascular and more stromal cells than in model group. Rats in model group had incomplete gastric mucosa, glandular disorders, reduction in the number of vascular and little stromal cells than in control group. Rats in treated group had yet complete gastric mucosa, glandular orders, abundant number of blood vessels and more stromal cells than in model group.4.2 Electron microscopy resultsRats in control group possessioned interstitial cell membrane integrity, abundant cytoplasm, normal mitochondria, endoplasmic reticulum and other organelles, complete nucleus and fine structure of the nucleus. Stromal cells at the rupture is not complete in model group rats with cytoplasmic reduction, only a small amount of residual organelles and incomplete nucleus. Rats in treated group had yet complete interstitial cell membrane, slightly reduced cytoplasm, complete nucleus and few organelles than in model group.5 The effect of Supplement Qi and Nourish Yin Resolve Masses and Dredge Meridians on stomach SCF/c-kit signaling pathway in GMD of DN rats.5.1 The expression of stomach c-kit mRNA among 5 group ratsThe expression of stomach c-kit mRNA was lower in model group than those in control group (P<0.05). The expression of stomach c-kit mRNA were lower in low dose treated group, middle dose treated group and high dose treated group than those in control group (P<0.05). The expression of stomach c-kit mRNA were lower in low dose treated group, middle dose treated group and high dose treated group than those in model group (P<0.05). The expression of stomach c-kit mRNA was lower in low dose treated group than those in middle dose treated group and high dose treated group (P<0.05).5.2 The expression of stomach SCF mRNA among 5 group ratsThe expression of stomach SCF mRNA was lower in model group than those in control group (P<0.05). The expression of stomach SCF mRNA were lower in low dose treated group, middle dose treated group and high dose treated group than those in control group (P<0.05). The expression of stomach SCF mRNA were higher in low dose treated group, middle dose treated group and high dose treated group than those in model group (P<0.05).Conclusion:1 Supplement Qi and Nourish Yin Resolve Masses and Dredge Meridians could promote gastric emptying and improve renal function and liver function and promote gastric emptying in GMD rats by decreasing BG and lipid.2 Supplement Qi and Nourish Yin Resolve Masses and Dredge Meridians could promote gastric emptying by decreasing the level of serum leptin and glucagon in DN GMD rats. It's not clear that the relation bettwen of GAS and GMD.The herbs could improve gastric function, which might not be correlated with the expression of leptin and OB-Rb in stomach.3 Antioxidant capacity reduced and oxidative stress enhanced in DN GMD rats. Supplement Qi and Nourish Yin Resolve Masses and Dredge Meridians could improve gastric emptying by anhancing antioxidant capacity and inhibitting the oxidative stress.4 Gastric mucosa and ultrastructure of gastric cajal interstitial cells were impaired DN GMD rats. Supplement Qi and Nourish Yin Resolve Masses and Dredge Meridians could improve gastric emptying by rehabilitating gastric mucosa and ultrastructure of gastric cajal interstitial cells.5 The expression of SCF and c-kit mRNA was decreased in stomach of DN GMD rats. Supplement Qi and Nourish Yin Resolve Masses and Dredge Meridians could improve gastric emptying by upregulating the expression of SCF and c-kit mRNA.6 The theory of'the same treatment for the different disease'is scientifically.
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