| Diabetic nephropathy (DN) is a part of diabetes'micrangium complication and one of the common reasons of end stage renal disease. Once the DN patient has continuity urine protein, the condition is to be irreversible, therefore, the positive effective treatment on early time DN and control DN progress are especially important. The modern medicine have not yet completely expounded to the cause and the development mechanism of DN, and no important breakthrough in treatment. The traditional Chinese medicine gradually demonstrates its superiority in the early DN's treatment. Professor Zhang gengliang Proposed early time DN's pathogenesis was qin yin liang xue and shen xu xue yu and establishs the treatment principle(Yi Qi Yang Yin Huo Xue method) of early time DN, accordinged to his Clinical Experience.Objective:In this research the model of diabetic rats were induced by intraperitoneal injection of streptozotocin (STZ). The diabetes mellitus( DM) rats were cure by the Chinese medical therapy of YiQiYangYinHuoXue method(YQM).Blood glucose, renal function, 24-hour urinary albumin excretion rate, kidney pathomorphology, kidney weight / body weight values, expression of Renal connective tissue growth factor(CTGF) were observed. The effect and mechanism of YQM on early time DN were investigated so as to provide experimental evidence .Methods: Fifty-eight healthy male Wistar rats with initial body weights of 160g to 200g were selected to our experiment. After one week, blood glucose and urine glucose were detected. The results were negative. Then they were randomly divided into five groups accordinged to the weight: Normal group(C,n=10),Model group(DM,n=12),YQMgroup(DM+Z,n=12), Irbesartan group( DM+I,n=12), YQM and Irbesartan group(DM+Z+I,n=12). The model of diabetic ,rats were induced by intraperitoneal injection of streptozotocin (STZ) except the Normal group.Tail vein blood glucose levels were measured after 72h. Rats with Blood glucose levels of more than 16.7mmol/l were selected as diabetic rats. The normal group rats was injected with a considerable volume of citromatic acid buffer. Into the mold after a week, Irbesartan group received 50mg/kg irbesartan orally once a day by gastric tube; YQM group received 33.5mg/kg YQM; YQM and irbesartan group the morning received the same dose of Chinese medicine, in the afternoon received to the same dose of irbesartan. Normal group is also given the same volume of tap water orally.During the experiment, the animals eating and drinking freely. 8 weeks after medication with the metabolic cages to collect 24-hour urine,measured by radio immunoassay urinary albumin, urinary albumin excretion rate calculation (UAER).The urinary creatinine was also determined. After eight hours of fasting, weighing,all animals were killed at 8 weeks after medication. Separation of serum,using automatic biochemical analyzer to detect the rats blood glucose (BG), blood urea nitrogen (BUN), serum creatinine (Scr).Weighed the weight of kidney and calculated hypertrophy index(KW/BW). After the left kidney fixed paraffin-embedded, cut into 4 thick slices line HE and PAS staining, sueing light microscope to observe morphological changes of renal pathology. Right kidney was Initial Fixed in 4% formaldehyde, conventional fixed, Paraffin-embedded sections, stand-by Immunohistochemistry to detect CTGF expression in renal tissue. All data are expressed by x±S, using One-way ANOVA,compiled statistics by the statistical software SPSS11.5.Results:1)During the experiment, the model group rats suffered from polydipsia, polyphagia, polyuria, weight loss and other symptoms of metabolic disorders, body hair reduced, messy, activity reduced; and occurs over time a variety of concurrent symptoms of diabetes. A variety of concurrent symptoms of diabetes occurred. The treated rats had improved the overall situation, of which the combination treatment group had the best results. (2)Kidney weight / body weight ratio in Model group was significantly higher than the normal group (P <0.01). The treatment group kidney weight / body weight ratio was significantly lower than model group, and there were significantly difference compared with the model group (P <0.01). Combination treatment group's renal hypertrophy index was significantly lower than Chinese medicine treatment group and Western medicine treatment group (p <0.01), and there was no significant difference between Chinese medicine treatment group and Western medicine treatment group.(3)Blood glucose levels of diabetic rats were significant higher than the normal group after modeling after injected streptozotocin (p <0.01). Chinese medicine treatment group and combination treatment group had hypoglycemic effect compared with the model group (P <0.01), and there was no significant difference between Western medicine treatment group and model group.(4)There was significant difference of BUN, Scr between Model group and normal group (P<0.01). Western medicine treatment group, Chinese medicine treatment group and Combination treatment group all can lower BUN, Scr levels, and there was significant difference compared with model group(P<0.01). Combination treatment group's levels of BUN, Scr was significantly lower than Chinese medicine treatment group and Western medicine treatment group (p <0.05).(5)Model group's 24h urinary albumin excretion rate was significantly higher than the normal group (P <0.01). 24h urinary albumin excretion of Western medicine treatment group, Chinese medicine treatment group and Combination treatment group were all lower than model group. Combination treatment group's 24h urinary albumin excretion rate was significantly lower than Western medicine treatment group and Chinese medicine treatment group (p <0.01). There was no significant difference between Western medicine treatment group and Chinese medicine treatment group (P> 0.05). Combination treatment group was more protective of DN than Western medicine treatment group and Chinese medicine treatment group (p <0.01).(6)In normal group, observed by light microscope after HE, PAS staining, renal glomerulus was integrity, no increase in renal glomerulus, no significant abnormalities in Glomerular capillary basement membrane and Mesangial matrix. In Model group, observed by light microscope after HE, PAS staining, renal glomerulus was increased, glomerular capillary basement membrane thickened, mesangial cell proliferation, mesangium widened. Three treatment groups had different levels of mitigation compared with model group, especially in Combination treatment group.(7)CTGF protein expression in model group were significantly higher than in normal group (P <0.01). CTGF protein expression in the treatment group were significantly lower than in model group (P <0.01); CTGF protein expression in Combination treatment group were significantly lower than Western medicine treatment group and Chinese medicine treatment group (P <0.05). YQM and Irbesartan's protective effect on DN, possibly by down-regulating the expression of CTGF, but can not completely block its expression, and their combination has a synergistic effect.Conclusions:1 YQM can improve the general status of diabetic rats , reduce the emission of urine protein, and protect the kidneys2 YQM were similar to irbesartan in intervention. YQM was better than irbesartan in the hypoglycemic.3 YQM and irbesartan can suppress CTGF's expression,ut union use of YQM and irbesartan was better. Union use of Chinese medicine and Western medicine has the stronger protective effect on DN. Its mechanism was partially related with the suppress of CTGF's expression and provided a new way for the cooperation of Chinese and Western medicine to prevent DN .
|
PDF Full Text Request