Based On The Theory Of Liver And Kidney Homologous Chai Huangyi Renal Granular Prevention Of The Complications Of Diabetes, Liver And Kidney Mechanism Research

Diabetic liver disease (DLD) is a hepatic complication of diabetes, which is mainly characterized as abnormality of liver histology or liver function, the serious patients would develop to liver fibrosis or cirrhosis. Diabetic nephropathy(DN) is a common complication of diabetes, which has been one of main cause leading to end-stage renal disease. With the prevalence of diabetes in China, recent epidemiological data revealed20.0-30.9%diabetics suffering from DLD and33.4%diabetic patients complicated with renal impairment. These two complications have been seriously problems of public health. There was few good therapeutic methods in treating the two diabetic complications with modern medicine respectively, which traditional Chinese Medicine(TCM) exhibit some advantages in preventing and treating the two complications dueing to the characteristics of holistic regulation and multiple targets. So we made classification and summary of the theory of homogeny of liver and kidney, then analyzed the application of the theory in recognition of pathogenesis and ideas for diagnosing and treating the two complications based on our previous studies. We also observed the effects of ChaihuangYishen granule(CHYS) on liver injuries and renal impairment in diabetic rats and investigated the common mechanisms of CHYS in treating the two complications, which will be beneficial to develop new drugs of treating the two complications and provide experimental evidences for the theory of homogeny of liver and kidney.Objective:To investigate the application of the theory of homogeny of liver and kidney in understanding the pathogenesis and ideas of diagnosis and treatment for the two complications. Under the direction of the theory, to study the usage of CHYS in treating liver injuries and renal impairment associated with diabete and clarify the common mechanisms of CHYS in treating the two complications.Methods:1. We investigated theoretic evidences of treating liver and kidney complications of diabetes based on the theory of homogeny of liver and kidney by utilizing the method of retrospective study of literature. The literature were consulted and arranged from various kinds of literature database and ancient medical classic by using of key words including "kidney and liver","liver and kidney","homoly of liver and kidney","homoly of Yi and Kui","homoly of essence and blood","concurrent diseases of liver and kidney"and "concurrent treatment of liver and kidney", which were relevant to homogeny of liver and kidney. We analyzed academic origin, development and evolution of the theory of homogeny of liver and kidney according to firstly time sequence and secondly representative books demonstrating the theory of homogeny of liver and kidney. By these work, we summarize the treatment regularity of treating diseases based on homogeny of liver and kidney. This will be beneficial to the recognition of etiology and pathogenesis of liver and kidney complications of diabetes and guiding therapeutic ideas of the complications with the theory of homogeny of liver and kidney.2、The effect of Chaihuangyishen Granule (CHYS) on liver injuries and renal demage in diabetic rats:Diabetes was induced by by right-kidney nephrectomy plus peritoneal injection of streptozotocin (40mg/kg) in male Wistar rats, diabetic rats were randomly divided into model group, CHYS group (2.24g/kg) and monopril (1.67mg/kg), Twelve rats with same age and gender were received an sham operation plus peritoneal injection of vehicle and usd as sham group. All animals were orally administrated once daily for20weeks. Body weight and animal behaviors were observed every week, blood glucose and24-h urinary protein were determined every4weeks. The levels of serum lipid(TC, TG) and liver function(ALT, AST) were detected by blood biochemistry meter. Pathological changes of liver and kidney were observed by semiquantitative assessment. The mRNA expression of TGF-β1, decorin and GLUT-1in the liver and kidney were measured by RT-PCR; the protein expression of TGF-β1and decorin in the liver and kidneys were detected by western blot. The expression of collagen I in the liver and kidney and hepatic collagen III expression were analyzed by immunohistochemistry.Results:1. Theoretic evidence of treating liver and kidney complications of diabetes based on homogeny of liver and kidney:Theory of homogeny of liver and kidney originated from Inner Canon of Huangdi, Clinical practice replenish and the theory in Han, Tang, Jin and Yuan dynasty, Comlete system of the theory formed in Ming and Qing dynasty. The theory revealed close relation of between liver and kidney, these two organs indidate p physiological promotion each other, while show mutual effect and transmission under pathological condition. Diabetes could induce liver and kidney complications, and clinic features or development of these complications were in line with pathological characteristic of concurrent disearse of live and kidney. So it is helpful for promotion of treating liver and kidney complications of diabetes with TCM under the guideline of the theory of homology of liver and kidney. 2. Improving effects of CHYS on live injuries in diabetic rats. Body weight of model group was significantly lower than that of sham group at weeks4(p<0.05), the difference reached an peaking at weeks20. There was significant difference in the level of blood glucose between model group and sham group during the whole experiment period(p<0.01); treatment with CHYS or monopril didn’t effect the levels of body weight and blood glucose. Serum levels of TC, TG, ALT and AST in model group showed obvious raise compared to those in sham group, while there was remarkable reduction of serum AST, TC and TG levels in CHYS group and monopril group. Index of liver weight and hepatic histologic active scores of inflammatory in model group were significantly higher than those in sham group, treatment with CHYS could alleviate these parameters(p<0.05).3. Attenuation of CHYS on renal impairments in diabetic rats. The level of24-h urinary protein of model group exhibited progressive elevation at weeks8(p<0.05), CHYS exerted significant decreasement of24-h urinary protein from weeks12(p<0.05), and monopril could reduce the level of24-h urinary protein at weeks16and weeks20(p<0.05). Percentage of mesangial matrix and tubulo-interstitial fibrosis index in model group were obviously higher than that in sham group(p<0.01), CHYS and monopril improved the abnormalities of the indices in diabetic rats(p<0.05).4. Effects of CHYS on expression of TGF-β1、decorin及GLUT-1in the liver and kidney of diabetic rats. Compared to that of sham group, hepatic expression of TGF-β1, decorin and GLUT-1mRNA were significantly increased; while CHYS group were statistically lower than that of model group(p<0.01). The increased expression of TGF-β1and decorin protein in the liver and kidney of diabetic rats were inhibited by CHYS or monopril treatment(p<0.05). The results of immunohistochemistry revealed the upregulation of collagen I expression in the liver and kidneys of diabetic rats(p<0.01), hepatic collagen III expression also remarkably raised in model group(p<0.05), and these changes were reversed by CHYS treatment; By PAS staining and d-PAS staining, we also observed accumulation of hepatic glycogen in model group, and CHYS could reduce hepatic glycogen storage in diabetic rats.Conclusion:1. The theory of homogeny of liver and kidney is important to understand etiology and pathogenesis of liver and kidney complications of diabetes and could be used for guiding the treatment of the two complications. 2. CHYS exhibited good therapeutic effects on both liver injury and renal impairment associated with diabetes, which reflect the advantages of multiple targets and holistic regulation of TCM.3.CHYS could inhibit expression of TGF-β1and decorin in the liver and kidney of diabetic rats and reduce the degree of fibrosis, which involves the common machanisms of CHYS in treating liver and kidney complications of diabetes.