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Protective Effect Of Houttuynia Cordata Thunb On Early Nephropathy Of Diabetic Rats And Its Molecular Mechanism

Posted on:2007-07-25Degree:DoctorType:Dissertation
Country:ChinaCandidate:F WangFull Text:PDF
GTID:1104360212990202Subject:Integrative basis
Abstract/Summary:PDF Full Text Request
Chapter1 Effects of Houttuynia cordata Thunb on Early Nephropathy in Type 1 Diabetic RatsObjectiveIn order to explore the effect of therapeutic method of clearing-heat and detoxification in traditional Chinese medicine on diabetic renal complication, the study was carried out to investigate the effects of Houttuynia cordata Thunb (HCT) on lipid metabolism and kidney function in type 1 diabetic rats.MethodsMurine type 1 diabetic model was induced by the intravenous injection of streptozotocin and the modeled rats were randomly divided into 5 groups: model group, HCT group, astragalus group, HCT add astragalus group, lotensin group, and normal rats without any treatment were set as normal control group. The modeled rats were treated correspondingly with distilled water, HCT, astragalus, HCT add astragalus, lotensin according their grouping for 8 weeks. Serum TC, TG, HDL-C and LDL-C levels, clearance creatinine, 24h total albumin and 24h β-2 microglobin in urine were determined. ResultsCompared with normal group, murine body weight and insulin level decreased while serum glucose increased significantly in model groups (P<0.01), and furthermore the levels of TC, TG, LDL-C elevated while HDL-C reduced obviously (P<0.05). In comparison with model group, serum levels of TC, TG, LDL-C were decreased (P<0.05) and HDL-C increased in the four treated groups (P<0.05), but there was no statistical difference among these treated groups (P>0.05).It was further demonstrated that albumin in 24h urine and beta 2 microglobin in 24h urine and clearance creatinine increased significantly in model group in comparison with normal group (P<0.05), while the above-mentioned parameters in the four treated groups were remarkably decreased as compared with model group (P<0.05), and there was little difference of those parameters among the four treated groups (P>0.05).Compared with normal group, the glomerular area and the ratio of kidney weight to body weight increased obviously in model group and the other treated groups (P<0.05). Compared with model group, there was no significant difference in K/W ratio among HCT, astragalus, HCT add astragalus, and lotensin groups, but the murine glomerular areas in treated groups decreased significantly (P<0.05), and there was no obviously difference among the treated groups (P>0.05).ConclusionIt is suggested that Houttuynia cordata Thunb might regulate the lipid metabolism in diabetic rats, through which it could decrease the levels of TC, TG and LDL-C and increase HDL-C level. It is also implicated that HCT decoction could protect the kidney function in diabetes rats in view of its reducing the excretion of urine albumin, beta2 microglobin, and clearance rate of creatinine. It could be further inferred that Houttuynia cordata Thunb, like Astragalus membranaceus Bunge and lotensin, might realize its protective effects on renal function through its decreasing the high filtration, high infusion and high permeability of glomeruli in murine early diabetic nephropathy. Chapter 2 Exploration on Protective Effects of Houttuynia Cordata Thunb on Murine Type 1 Diabetic NephropathyObjectiveTo examine the expression of TGF-beta 1, HGF and NF-kappa B and so on in kidney tissue of diabetic rats and to explore the mechanism of Houttuynia cordata Thunb on kidney protection in diabetes rats.MethodsThe type 1 diabetes rat model was induced by the intravenous injection of streptozotocin and the modeled rats were randomly divided into 5 groups and treated with HCT, astragalus, HCT add astragalus, lotensin and saline respectively for 8 weeks. The expression of TGF-beta 1, HGF and NF-kappa B so on in kidney tissue in diabetes rats were determined with imminohistochemistry and RT-PCR.ResultsCompared with normal group, the expression of NF-kappa B, TGF-beta 1, HGF, Collagen I and its mRNA increased significantly, expression of BMP-7 and its mRNA descreased obviously in diabetes model group and the four treatment groups (P<0.05). In comparision with diabetes model group, the expression of NF-kappaB, TGF-beta 1, Collagen I and its mRNA was down-regulated and while the expression of HGF, BMP-7 and its mRNA was up-regulated significantly in the four treatment groups (P <0.05). Regarding the these parameters, there was no obviously difference among the four treatment groups (P >0.05).ConclusionThe result suggested that HCT might protect the kidney tissue of diabetic rats through reducing the expression of NF-kappa B, TGF-beta 1, Collagen I and its mRNA and upregulating the expression of HGF, BMP-7 and its mRNA.Chapter 3 Protective Effect of Houttuynia Cordata Thunb on Murine Type 2 Diabetic Nephropathy and Its MechanismObjectiveTo investigate the effect of Houttuynia cordata Thunb (HCT) on type 2 diabetic nephropathy and the expression of TGF-beta 1, HGF, BMP-7, Collagen III, NF-kappa B in kidney tissue of type 2 diabetic rats.MethodsMurine model of type 2 diabetes was induced by injecting small dose STZ and high lipid and hign glucose forage. The modeled rats were randomly divided into model, HCT, aspirin, berberine groups treated correspondongly by gastrogage for 8 weeks. The murine blood lipids and kidney function were determined. Expression of TGF-beta 1, HGF, BMP-7, Collagen III, NF-kappa B in diabetic kidney were checked.ResultsCompared with normal control group, the serum levels of TC, TG, FFA increased in type 2 diabetes model group, meanwhile total 24h albumin, beta 2 microglobin in urine and clearance creatinine descreased. Compared with model group, the levels of TC, TG, FFA in HCT, aspirin and berberine groups were significantly lowered, but there was no statistical difference among the treatment groups. The expression of TGF-beta 1, NF-kappa B, HGF, Collagen III increased and BMP-7 decreased in type 2 diabetes model group, as compared with normal group. Compared with model group, the expression of TGF-beta 1, NF-kappa B, Collagen III in HCT group decreased while HGF and BMP-7 increased significantly, but among the treatment groups, there was no statistical difference.ConclusionHCT could regulate lipids metabolism and improve insulin sensitivity, protect kidney function. The therapeutic mechanisms might be closely correlated with its improving insulin resistance and up-regulating the kidney expression of HGF, BMP-7 and downregulating the expression of TGF-beta1, Collagen III and NF-kappa B.
Keywords/Search Tags:Houttuynia cordata Thunb, Diabetes, Dyslipidemia, Kidney, diabetic nephropathy, transforming growth factor beta 1, hepatocyte growth factor, nuclear transcription factor kappa B, bone morphogenetic protein-7, Type 2 Diabetes, Kidney disease, TGF-beta 1
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