Astragalus Euonymus Mixture Of Endothelial Cell Injury In Diabetic Nephropathy Intervention

Diabetic nephropathy, (DN) is an important microvascular complication of diabeticmellitus (DM) as well as the common reason resulting in chronic renal failure. DN whosepathogenesis has not been fully understood, doesn't been well treated in the days. It is verysignificance to find a effective method of treatment to DN. Systematic studies on theprevention and treatment for DN by HuangQiWeiMao Mixture (HQWM Mixture) had beenperformed from theaspects of referencereviews, theoryand experimental studyinthis essay.westudytheHuangQiWeiMaoMixturepreventDNkidneyendothelialcellsfromlesion.1ReferencereviewThis essay reviewed from the advances of such fields as follwed:The results andprogresses of studyon the pathogenesis and Medication for DN, the method of investigate ofmodern medicine, mechanism of action of prevention and cure DN with traditional Chinesemedicine, the relationship of DN and EC, foundation of the experimental DN animal model.2TheorystudyBy discussing the pathogenesis theory, principle and method of treatment of Xiao keBing nephrosis with Chinese medicine theories quoting from classics works and combiningmodern research result, we put forward and perfect the theory that deficiency of kidney andimpairment of both QI and YIN are the origin, however qi-stagnancy and blood stasis andphlegmatic hygrosis stay in the body are indications, pathogen usually intruding intocollateral in protracted disease and ZhengJia generate in kidney are the key point.We initialIlluminate the relationship of WeiXingZhengJia hypothesis and endothelial cell lesionmechanism, quibus establish the effective way of"Method of invigorate Qi and activateblood circulation, removing cumulation and stasis"is the fundamental therapeutics to DN ,gisttoprovidthetheoryofstudymethodandresearchtocureDN.3ExperimentalstudyPURPOSE: Study the HuangQiWeiMao Mixture prevent DN kidney endothelial cellsfromlesionandmechanism.METHODS: We used DM glomerulosclerosis rats model induced by unilateralnephrectom and injecting streptozotocin(STZ) , then divide them randomly into modelgroup(M),experimental group (H) in HQWM Mixture, positive control group(K) , shamoperated group(F) was blank group . Observed the rats common condition , and examinedrats weight, urine volume , fasting blood glucose, glycosylated hemoglobin(HbA1c),blood-fat , 24h Urine protein quantitation, renal function per month dynamicly . Observeglomerulus and renal tubule mesenchymal morph, peripheral vessels(PCT) use lightmicroscope; detected serum laminin(LN)and typeⅣcollagen content used enzyme linkedimmunosorbent assay(ELISA) method; examined nitrogen monoxidum (NO) content ofnephridial tissue through nitrate reductase; deted endothelin-1(ET-1) by radio-immunity method; observed the express of hepatocyte growth factor(HGF) and transforming growthfactorbeta1(TGF-β1)innephridialtissuebywesternblot.RESULTS:①The results showed HQWM Mixture obviouslyimprove the rats'generalcondition and had a certain effect on reducing blood sugar, serum cholesterol (TC) andtriglyceride (TG), low density lipoprotein (LDL), which had a significant statistic sense incomparing with diabetic model group (P<0.05, P<0.01). as well as it can decrease theexperimental rats'higher serum urea nitrogen, creatinine,it also reduced experimental rats'24h Urine protein evacuation, Which had a significant statistic sense in comparing withdiabetic model group (P<0.05). The results indicated that HQWM Mixture was beneficial forregulating glucose and lipid metabolism, decreasing Urine proteinand excretion improvingrenal function. Surpass positive control therapeutic effect especially in regulating glucose,lipid metabolism and improving renal function. But it didn't as good as positive control indepress 24h Urine protein, have no statistically significant (P>0.05). The changes of renaltissue morphology in experimental diabetic rats were observed by optical microscope , theconsequence showed that the model group Glomerular mesangium diffuse widen ,extracellular matrix (ECM) increased, basement membrane became thicken.The above-mentioned pathology changes relieved significantly after the treatment by HQWM Mixture,which hinting that it can protect DN rats kidney. While Cozaar can also protect renalglomeruli.②TheconsequenceofELISAtestshowedthat DNrats secretedandsynthesised LN andtypeⅣcollagen increasingly, which revealingthe kidneyof DN rats damaged at some level.HQWM Mixture and Cozaar can both degrade LN and typeⅣcollagen contents,HQWMMixture group have an advantage effect in reducing typeⅣcollagen, while it didn't showbetter in LN (P>0.05). We can conclude that HQWM Mixture can decrease glomerulisecreting LN and typeⅣcollagen contents, which maybe one of its mechanism of action topreventandcureDN.③Studying the content of NO in the experimental animals'renal tissue with nitratereductasetestandET-1withradioimmunoassay,theresultsshowed:thecontentofNOinDNmodelgroup'srenaltissueobviouslydecreased(P<0.01),whilethecontentofET-1increasedsignifycantly. It hinted that kidney endodermis cell lesion and imbalance of NO and ET-1.After the therapy of HQWM Mixture and Cozaar, the content of NO increased andET-1deduced obviously, which have remarkable difference from the model group (P <0.05);WecanconcludethatHQWMMixturecanblockatleastpartlyblockDNratsEClesion.④ItwasdonethatassayingtheproteinexpressionofHGF,TGF-β1 inexperimentalrats'renaltissueofeachgroupbywestern-blotmethod.Theresultsshowed:theproteinexpressionof HGF in DN model group's renal tissue obviously decreased, while the protein expressionof TGF-β1 increased significantly comparing with sham operated group (P<0.05). After thetherapyofHQWMMixtureandCozaar,theproteinexpressionofHGFincreasedandTGF-β1 increased significantly, which can adjust the dynamic equilibrium of HGF and TGF-β1,furthermore,itcanhold-backtheECdamageofkidneyandcanpromotekidneytissuerepair.Conclusion: HQWM Mixture of"method of invigorate Qi and activate bloodcirculation, removing cumulation and stasis", which aimed directly at"WeiXingZhengJia",pathogenesis, canpreventionandcurediabeticnephropathyutilitily. Thepossiblemechanismof action is beneficial for regulating glucose and lipid metabolism, decreasing Urineproteinand excretion improving renal function, lessen nephridial tissuedamage, suppressormajor extracellular matrix such as LN and typeⅣcollagen, modulation EC correlated cellfactors dynamic equilibrium such as NO, ET-1, HGF, TGF-β1. This study explores themechanismofHQWMMixtureintreatingDNonamultitargetandmulti-elementbasis.