Intervention Study Of Jiedutongluobaoshen Capsule On The Relationship Between Renal Microinflammation And Adiponectin In Experimental Diabetic Rats

PurposeDiabetic nephropathy (DN), called XiaoKe nephrosis in the traditional Chinese medicine, is one of the common and serious complications of diabetic mellitus (DM). DN, known as glomerulosclerosis, belongs to glomerulopathy caused by microangiopathy of DM, which has become the main etiological factor for the end-stage renal disease (ESRD). In the clinic, the early change of DN is appearing urine microalbumin, and then, it appears the clinical albuminuria, ultimately, it get into chronic renal insufficiency. DN is a chronic progression, and its main pathological changes are glomerular hypertrophy, the thickening of the glomerular basement membrane, the intercapillary cells hyperplasy, mesargial area extracellular matrix (ECM) accumulation, tubule hypertrophia, and glomerulosclerosis. The DN pathogenesis is so complex that it has not been completely clarified until now. At present, there are no more effective treatment and prevention methods to control it. The recent experiment and clinical research have indicated, even if taking all the remedial measures to DN, that blood glucose, blood pressure, and blood fats were controlled in the ideal levels, only parts of DN patients would postpone disease progress, and most DN patients are still facing the slow progresses to the final stage renal failure. More and more experiments and the clinical practice indicate that the micro inflammation (the low grade inflammation) reaction has certain effects on the DN pathogenesis, and has provided the rationale in the anti-inflammation treatment for the DN. Adiponectin secreted by adipose tissue has the close relationship in the DN pathogenesis and progression. The reducing contents of adiponectin activate NF-кB, induce the expression of MCP-1, which stimulate mononuclear macrophage to accumulate and activate in kidney.MethodsThis essay was performed systematically in theory and experimental studies about the DN for the traditional medicine JieDuTongLuoBaoShen capsule (JDTLBS capsule). The key points were the pathogenesis theory about poisonous damaging the kidney meridian, the correlation between the inflammation pathogenesis of DN and adiponectin, and the effects of JDTLBS capsule in the inflammation pathogenesis and adiponectin. It showed the superiority and science of the traditional Chinese theory and the JDTLBS capsule in curing the DN, which may be a new point of view to explain the DN pathogenesis.This experiment studied the renal microinflammation pathogenesis using the JDTLBS capsule in the experimental diabetes rats, discussed the capsule's effects in renal protective mechanism and the relationship between the JDTLBS capsule treatment and adiponectin, which may provide a perfect theory basis in curing and preventing DN. This experiment was included four parts:1. The method of construction the model of the diabetic rats adopt to the hyper-lipoid raised and STZ-injected. And then, these rats were divided into normal control group, hyper-lipoid group, diabetic model group, positive control group, and experimental group with Chinese herb. For studying renal protective effects of the capsule, the diabetic rat condition was observed, blood biochemical indicators were detected, the urine microalbumin with the biochemistry, enzyme linked immunosorbent assay methods.2. The pathomorphology in renal tissue of experimental diabetic rat was observed by optical microscope and electric microscope, and the deposition of fibronectin (FN) and collagen IV(Col IV), the expression of extracellular matrix (ECM) in renal mesangial region was dermined by the immunohistochemisty method.3. The effects of JDTLBS capsule on the protein expression adiponectin in serum and renal tissues of experimental diabetic rats and the gene expression of adiponectin recepor1 (AdipoR1) and adiponectin recepor2 (AdipoR2) were detected by enzyme linked immunosorbent assay (ELISA), immunohistochemical and RT-PCR methods.4. The effects of JDTLBS capsule on the protein and gene expression MCP-1 in renal tissues of experimental diabetic rats were detected by immunohistochemical and RT-PCR methods.Results1. JDTLBS capsule improved the condition of experimental diabetic rats, and reduced blood glucose levels and regulated blood fat.2. JDTLBS capsule protected the kidney by inhibiting therenal hypertrophy in early stage of experimental diabetic rats, and reduced the urine microalbumin excretion. 3. JDTLBS capsule inhibited the lesions of renal pathomorphology, ultrastructural changes, relieved protein expression of FN and ColⅣin the renal tissue, and decreased accumulation of extracellular matrix, suggesting that JDTLBS capsule improved glomerular sclerosis of DM, and postpone DN progression4. JDTLBS capsule increased the serum adiponectin contents and adiponectin protein and gene expression in diabetic rats, meanwhile, the expression of AdipoR1 is higher than AdipoR2 in renal tissue.5. In the diabetic rats, model by both hyper-lipoid raised and STZ-injected, the renal tissue protein and gene expression of MCP-1 were increased, which showed that the renal microinflammation has an important effect in the DN pathogenesis. The expression MCP-1 had a negative relationship bewteen serum adiponectin contents and adiponectin expression in the renal tissues.6. JDTLBS capsule obviously inhibited the protein and gene expression MCP-1 in renal tissue of experimental diabetic rats. The anti-inflammation pathogenesis of JDTLBS capsule could decrease the multi-expression of MCP-1 by increasing adiponectin contents, inhibiting NF-кB activation.ConclusionsThis experiment shows that treatment of JDTLBS capsule reduces blood glucose and regulates blood fat in experimental diabetic rats;inhibits the renal microinflammation reaction;increases serum adiponectin contents, adiponectin protein and gene expression in the renal tissues;relives hurt in renal construction, improves renal function, and postpone glomerular lesions of DM.This experimental innovation spot is to consummate traditional Chinese theory of removing toxicity, smoothing meridian, and protecting kidney, and bring the DN pathogenesis of microinflammation into this traditional theory for discussing the association of Chinese medicine theory of poisonous damaging the kidney meridian towards the adiponectin, adiponectin receptor and their regulating DN microinflammation pathogenesis. Applying the above research into DN study is a new presumption, which may become a new point to curing DN, and provide a new pathway for prvention and thrapy of DN using the JDTLBS capsule...