Role Of Matrix Metalloproteinase-2 (MMP-2) In The Development Of Renal Fibrosis And Effect Of Shuxuetong On Renal Fibrosis

Background: Different kinds of progressive type kidney diseaseshould result eventually in glomerular sclerosis or renalinterstitial fibrosis and round into chronic renal failure. For themoment, though the application of manifold remedial measures suchas controlling blood pressure, inhibiting renin-angiotensin systemactivity, restricting diet and different kinds of etiology treatmentand so on, for majority patients, it isn′t able to postponeeffectively evolutional rate of glomerular sclerosis and renalinterstitial fibrosis. Therefore, in order to improve glomerularsclerosis and renal interstitial, postpone development of chronicrenal failure, ameliorate prognoses of different kinds of kidneydisease and enhance survival rate, it is very necessary to study anew remedial avenue.Objective: To study the actions of matrix metalloproteinase-2(MMP-2) in the development of the renal fibrosis, evaluate thediagnose value of blood MMP-2 concentration in the renal fibrosisand research treatment of Shuxuetong on renal fibrosis.Methods: The objects were 33 patients of chronicglomerulonephritis, with a definite diagnosis based on renal biopsyfrom 2004.3 to 2005.7 in our hospital. To exclude impact of resultingin elevation on blood MMP-2 concentration, it is necessary to selectthe patients with primary glomerulonephritis. 33 chronic glomerulardisease patients were cut into proliferation group(18 cases) andfibrosis group(15 cases including glomeruloselerosis) according torenal fibrosis degree in the renal pathology. Setting another 8health human cases as control group. The serum sample of all researchobjects were gotten to measure the level of pro-MMP-2 and MMP-2concentration in serum with the method of SDS-PAGE enzymography. Thencompare the level of pro-MMP-2 and MMP-2 in serum among every group.The second study is about to the treatment of Shuxuetong on renalfibrosis. The objects is anterior fibrosis group(24-hour urineprotein amount of all patients was less than 3.5g;all patients didn′ t applicate other medicine). The objects were divided intopre-treatment and post-treatment. Detect and compare the laboratoryindexes of two groups, including serum pro-MMP-2 and MMP-2 , 24-hoururine protein amount, serum lipid, serum creatinine, fibrinogen,fibre connexin. Multiple interclass materials data comparision isbased on mean square analysis and LSP-t to examine.If P<0.05, itis significant on statistics.Results: Serum MMP-2 level was much higher in proliferation groupthan control group(P<0.01) and lower in fibrosis group than controlgroup(P<0.05). There isn't obvious difference on serum pro-MMP-2level(P>0.05). After the treatment of Shuxuetong,the level of serumMMP-2, lipid and creatinine decreased(P<0.05), 24hours urinaryprotein amount, serum fibrinogen significantly decreased(P<0.01).There were no significant differences in serum pro-MMP-2 in bothpre-treatment and post-treatment(P>0.05).Discussion: The majority of specialists and scholars consideredthat MMP-2 is correlated with the pathogenesis of renal fibrosis.Our study detected that there are significant increase of level ofserum MMP-2 in proliferation group(P<0.01), whereas there aredecreased in fibrosis group(P<0.05). This indicated that there areprobably double action in inflammatory nephropathy. If MMP-2expression increased, it will be able to destroy glomerular-basementmembrane and impact remodeling of convalescence glomerulinormal structure. If MMP-2 expression decreased ,it will be able toglomerular mesangial matrix stack, eventually lead to glomerularsclerosis and renal interstitial fibrosis. In a word, there is aclearly poles apart concentration change of serum MMP-2 in vary stateof inflammatory nephropathy development. Therefore to detect theserum MMP-2 concentration can have a certain diagnostic value in theearly stage of all kind of renal glomerular disease. It can conductas a screening detect marker before renal biospy.Nephritis ofpatients with definite glomerular sclerosis and renal interstitialfibrosis in pathology were cure rully, this study suggest that thecontent of urine protein of nephritis of patients treated byShuxuetong decreased obviously(P<0.01), but is not equal to thecontent of normal control. We can conclude that Shuxuetong used totreat nephritis alone can decrease the urine protein, but can notmake a total recovery. If matched with drugs such as adrenal corticalhormone, there are possibility of treatment is short. The level ofserum MMP-2 of nephritis of patients treated by Shuxuetongincreased(P<0.05). We can conclude that Shuxuetong can protectkidney through interfering MMPs/TIMPs system. But the biologicalactivity of MMP-2 is modulated by many factors: such as TGF-β, IFN-α,γ, IL-1α,β, TNF-α, bFGF and so on. So the way of Shuxuetongto interfere with the expression of MMP-2 should be studied further.In conclusion, Shuxuetong plays a important role in treatingglomerulonephritis. It provides not only a new method to cure renalfibrosis, but also the further clinical proofs to develop and applyShuxuetong to experimental study.Conclusion: 1. There is a significan difference between sufferinggroup and normal control group in serum MMP-2. The level of serumMMP-2 in proliferation group is higher than control group, and lowerin fibrosis group. Therefore to detect the serum MMP-2 concentrationcan understand development of disease and estimate prognoses. 2.Fromthe clinic curative effect, we can see that Shuxuetong decrease levelof serum MMP-2, 24hour urinary protein amount, serum lipid level.In conclusion, Shuxuetong plays a important role in improving renalfibrosis.