The Protective Effect And Mechanism Of The Mixture Of Radix Astragalus And Polygonum Mulflorum On Early Renal Injury In Rats With The Metabolic Syndromes (MS)

Part I The effects of the mixture of Radix Astragalus and Polygonum mulflorum on glucose and lipid metabolism and renal function in rats with MSObjective To investigate the effect of mixture Radix Astragalus and Polygonum mulflorum on glucose and lipid metabolism and renal function in rats with metabolic syndrome.Methods To establish experimental metabolic syndrome rat model through a high-sugar and high-fat diet, Animals were administered with the mixture of Radix Astragalus and Polygonum mulflorum (low dose group, middle dose group and high dose group). At the8th week, the serum were used to detect TG、TCH、Scr、Bun、 UA and Glu with biochemical analyzer, the pathologic change of kidney was observed by light microscopeResults At the end of8th week,In MS model group, there is a significant increase in body weight, serum glucose, cholesterol, triglycerides and low density lipoprotein, and accompany with the significant decrease of high-density lipoprotein and insulin sensitivity index, those satisfied the diagnostic indications of MS. The body weight of rats treated with the mixture of Radix Astragalus and Polygonum mulflorum was decreased significantly compared with model group, and there is similar results in rats treated with Metformin(P＜0.05); Radix Astragalus and Polygonum mulflorum mixture can significantly reduce serum levels of TCH, TG and LDL (P＜0.05), at the same time the serum level of HDL-C increased significantly (P＜0.05); there is significant change on Scr、BUN and UA in experimental rat treated with the mixture of Radix Astragalus and Polygonum mulflorum (P<0.05), the pathologic change was improved after treatment.Conclusion:The model of metabolic syndrome in rats can be successfully replicated through High-sugar and high-fat diet. The mixture of Radix Astragalus and Polygonum mulflorum can improve insulin sensitivity, and regulate lipid metabolism, reduce blood glucose, and protect renal function. Above all it can improve the pathologic change in MS rats. Part II The effects of the mixture of Radix Astragalus and Polygonum mulflorum on renal secretion of AngⅡ and FFA and oxidative stress in rats with MSObjective To investigate the effect of the mixture of Radix Astragalus and Polygonum mulflorum on renal secretion of angiotensin Ⅱ (AngⅡ) and free fatty acids (FFA) and oxidative stress in rats with metabolic syndrome.Methods To establish experimental metabolic syndrome rat model through a high-sugar and high-fat diet, Animals were administered with the mixture of Radix Astragalus and Polygonum mulflorum (low dose group, middle dose group and high dose group). At the end of8th week, the level of Super Oxygen Dehydrogenises (SOD) and Methane Dicarboxylic Aldehyde (MDA) in the serum and renal cortex were determined by colorimetric method, the level of AngⅡ and FFA in the serum and renal cortex were detected by radioimmunoassay.Results The enzyme activity of SOD in the serum and renal cortex was decreased significantly in rats with MS (P＜0.01), on the contrary, the level of MDA、AngⅡ and FFA in the serum and renal cortex were increased significantly (P＜0.01). After treated with the mixture of Radix Astragalus and Polygonum mulflorum, The enzyme activity of SOD in the serum and renal cortex was increased significantly (P＜0.05), At the same time, The level of MDA、AngⅡ and FFA in the serum and renal cortex were decreased significantly (P＜0.05)Conclusion The abnormal secretion of FFA and AngⅡ were occurred in rats with MS, at the same time, the oxidative stress response was being aggravated. After treated with the mixture of Radix Astragalus and Polygonum mulflorum, the above abnormal change was improved, that might be its prevention and treatment mechanism of early renal injury in rats with MS. Part Ⅲ The regulation of mixture of Radix Astragalus and Polygonum mulflorum on balance of NO and ET-1in rats with MSObjective To investigate the effect on blood pressure and regulation of the mixture of Radix Astragalus and Polygonum mulflorum on the balance of Nitric Oxide (NO) and endothelin-1(ET-1) in rats with metabolic syndrome.Methods To establish experimental metabolic syndrome rat model through a high-sugar and high-fat diet, Animals were administered with Radix Astragalus compound mixture (low dose group, middle dose group and high dose group) for8weeks. Then, the level of SBP、DBP、MAP were detected with multifunction physiological monitor, The level of NO and the enzyme activity of NOS in the serum and renal cortex were determined by colorimetric method, he level of ET-1in the serum and renal cortex were detected by radioimmunoassay, The mRNA expressions of Renal ET-1and NOS were detected through reverse transcription polymerase chain reaction(RT-PCR).Results The level of SBP、DBP、MAP in MS rats was increased significantly compared with normal rats (P＜0.05), The enzyme activity of NOS and the level of NO in the serum and renal cortex and the renal gene expression of NOS was decreased significantly in rats with MS (P＜0.05), On the contrary, the level of ET-1in the serum and renal cortex and the renal gene expression of ET-1was increased significantly (P＜0.05). After treated with the mixture of Radix Astragalus and Polygonum mulflorum, The level of SBP、DBP、MAP in MS rats was decreased significantly compared with normal rats (P＜0.05),The enzyme activity of NOS and the level of NO in the serum and renal cortex and the renal gene expression of NOS was increased significantly (P＜0.05)(P＜0.05), At the same time, the level of ET-1in the serum and renal cortex and the renal gene expression of ET-1was decreased significantly (P＜0.05)Conclusion The balance of NO/ET-1was destroyed in rats with MS, and then the abnormal level of SBP、DBP、MAP were detected, The mixture of Radix Astragalus and Polygonum mulflorum can lower the blood pression in MS rats through to regulate the balance of NO/ET-1in MS rats, this might play key role in protection the early renal injury of MS rats. Part IV The effects of the mixture of Radix Astragalus and Polygonum mulflorum on renal expression of Podocin and Nephrin in rats with MSObjective To investigate the effects and mechanism of the mixture of Radix Astragalus and Polygonum mulflorum on early injury of renal podocyte in rats with metabolic syndrome.Methods To establish experimental metabolic syndrome rat model through a high-sugar and high-fat diet, Animals were administered with Radix Astragalus compound mixture (low dose group, middle dose group and high dose group) for8weeks. Then, the level of24hPro was detected by colorimetric method; the level of MA and ACR were detected by lmmunoturbidimetry; the protein expression of Nephrin and Podocin in renal cortex was determined by immunohistochemistry; the gene expression of Nephrin and Podocin in renal cortex was determined by RT-PCR; The pathological change of Glomerular Basement Membrane(GBM) and podocyte was observed by electron microscope.Results The level of24hPro、MA and ACR were increased significantly in rats with MS compared with normal rats(P＜0.05); Under electronic microscopic examination, fusion of foot process, disruption of GBM and enlargement of infiltration pores, thickness of GBM were observed; the protein and gene expression of Podocin and Nephrin in renal cortex was decreased significantly compared with normal rats(P＜0.05). After8weeks treatment with the mixture of Radix Astragalus and Polygonum mulflorum, The level of24hPro、MA and ACR were decreased significantly in rats with MS compared with normal rats(P＜0.05); the pathologic change of GBM and podocte was reduced significantly compared with MS rats; the protein and gene expression of Podocin and Nephrin in renal cortex was increased significantly compared with normal rats(P＜0.05).Conclusion The pathological change of podocyte was observed in rats with MS, accompanied by the abnormal protein and gene expression of Nephrin and Podocin in renal cortex. After the treatment of the mixture of Radix Astragalus and Polygonum mulflorum, the abnormal condition was improved, and it might play a key role in protection the early renal injury of MS rats.