The Mechanism Of Action Of Rhubarb Inhibiting MMPs On The Therapy Of Chronic Renal Failure

Chronic renal failure (CRF) is the continuously developed and serious stage of the chronic renal disease , is the common turnover that various kinds of etiopathogensis cause renal disease . It genesis on the foundation of various kinds of chronic renal parenchyma disease , emerge the renal function decres- cence and till failure . According to the inception rate and morbidity rate of the International Renal Disease Institution adding up on the partial of countries and regions , it indicated that the inception rate of CRF was an upgraded ten- dency in the scope of the whole world , especially the inception rate of USA (the patients of CRF kainogenesis every year) grew fastest , to 7.6%.It indicated that the attack rate incrased obviously in Asian countries and regions . It analysesed from the attack rate (the summation of kainogenesis and orthogenerous CRF patients ) that ,there was the highest growth rate of average case rate(7.4%) in Japen . The statistics in our coutry was not integrated , there were about ten thousands kainogenesis CRF patients who got the dialysis theraphy , over fifty to sixty thousands peoples that sustained hematodialysis or peritoneal dialysis.It made people anxious that the number of CRF patients was growing quickly. Lately, USA conjectured that the quantities both with disase and neopathy were grew , and then the totle number of CRF patients in USA would be over 660,000 on the basis of the numerical data by regression equation.The therapertics of CRF at present are pessimistic confront the enormous patients'group. It is only lessened the retention of metabolic product and intoxicant by commonly used dialysis temporarily. There are the adverse reaction in the nondialysis. And the kidney transplantation confines many patients'healing because of the expensive charge. The Traditional Chinese Medical method own the features that its history is long , its clinical experience is abundance,its adverse reaction is tiny,and its charge is low. Rhrbarb is the Chinese medicine commonly used in plenty of Chinese medicine that cure CRF.There is the theory basis and study perspective that rhrbarb cure CRF by investigation of the pharmacologic action, animal experiment, clinical test.In the meanwhile ,MMPs play a important biological part in the revision of glomerular membrane's indurascent and renal interstitium's gibrous degeneration. This experiment is based on the foundation above, approaching the mechanism of action of rahubarb trading CRF, presuming the type of MMPs that is inhibited by rabubarb,and the active componet of rabuharb.I adopt DQ-gelatin substrate as fluorescence substrate in this experiment, MMP-16 fluoresces before degrading the substrate,detecting the transmutation of the fluorescence intensity in the reaction system.The determination of inhibiting action is adding the rahubarb extractive in the reaction system, the inhibiting composition in the extractive cohere with MMP-16,occupying the active center of MMP-16,making the the substrate shouldn't cohere with MMP-16 ,inducing the velocity of degrading substrare lower and the change of fluorescence intensity stepping down. I couled get the status that the extractive of rhubarb inhibite MMP-16 by the change of fluorescence intensity representing the vital force that MMP-16 degrades the substrate. We should yield that the %inhibition that different concentration of rhubarb extractive inhibiting MMP-16.The experimental result indicates that there is the inhibitory action that the extractive of rhubarb acts on MMPs.It is effective and confirmed that rhubarb trading CRF from the clinical tests and experiments. Rhubarb is bitter in taste and cold-natured. Bitter makes decanta. Frigidity makes clearing away heat, transiting the lower jiao yang ming intestine and stomach and eliminating heat-evil. Rhubarb inhalans heart, liver and pericardium channels and collaterals ,eliminating the heat-evil and sluggish. On one hand, rhubarb is proper trading the sthenia syndrome and pyretic syndrome by compatibility other heat-clearing and detoxicating medicine.On the other hand , rhubarb is also proper trading the asthenia cold syndrome by compatibility strengthening body resistance medicine .Modern medicine presume that rhubarb should inhibit the glomcrulus intercapillary cells paraplasm , the production of TNF ,genic expression of TGF-βmRNA , and the accretion of ECM; amend the nitrogen metabolism of CRF patients, fatty substance metabolism;eliminate free radicle.It is discovered that the relationship between CRF and MMPs by the pathoinvestigation of CRF. The family of MMPs is the important enzyme system of degrading ECM. It is confirmed that mesangial cell, endodermis cells, splanchnic wall and parietal layer cellula epithelialis ,renal cells , infiltrative monocaryon macrophage and neutrocyte all express MMP-1,2,3,7, 9 ,10,and 11. TIMPs should bind with the catalytic activity zinc ion of MMPs specifily,and block the activity of MMPs. Mesangial cell , renal cell, renal interstitium collagenoblast and infitrative mononuclear macrophage all should produce TIMP-1.TIMP-1 should inhibit MMP-9(degrading basilemma collagenⅣ) and MMP-1 (degrading basilemma collagenⅠ,Ⅲ) ,so TIMP-1 express accentuatly ,the degrading of ECM attenuatly.It induces the production of glomerular sclerosis and renal interstitial fibrosis . Plenty of scholars already observed the TIMP-1 enhance expression in many kinds of renal disease. Besides, TIMP-2 should inhibit MMP-2 to attenuate degrading collagenⅣ,so the hypsiexpress of TIMP-2 should participate the production of glomerular sclerosis in renal disease.Based on the foundation above, it is concluded that rhubarb should inhibit MMPs, it probably is an important mechanism of action that rhubarb trading CRF.