The Mechanism Research Of Ecliptae Herba Accommodates The Imbalance Of Matrix Metalloproteinase System In Diabetic Nephropathy

Diabetic Nephropathy is one of the serious complications of diabetes. The basic pathologic change is the accummulation of the extracellular material of glomcrulus (ECM). Extracellular matrix (ECM) plays an important part in retaining structure and function of normal tissue and in the process of cell growth and differentiation. It is in the dynamic balance of metabolic turnover and degradation remodeling. The disharmony of ECM's dynamic balance is correlated intimately with many pathological processes in vivo, such as hepatic, artherosclerosis, kidney disease and tumor infiltration and recurrence.It will lead to the pathologic change of hypertrophia of acinus renis, thickening of basal membrane and distension of mesangial region, diffuse or nodosity hardening of glomcrulus etc. In the accommodation of metabolic balance of ECM's synthesis and degradation , the function of the two enzymatic systems of matrix metalloproteinase and tissue inhibitor of metalloproteinase is dramatic.Matrix metalloproteinase (MMP) is the important catabolic enzymes of ECM, it has the important place in ECM's degradation. Recently, Tissue inhibitor of metalloproteinase (TIMP) is a specific catastaltica, it is a negative moderator to MMP in ECM's metabolic regulation. The system of MMP/TIMP must play an significant role in the onset progress of Diabetic Nephropathy.there are three opionions about the mech how the ECM caused the Diabetic Nephropathy :MMP's decrease and TIMP's up-regulation, the main part of TIMP is TIMP-1;the enhance of MMP's expression and the enhance both of MMP's and TIMP's expression.Diabetes belongs to Diabetes in TCM. The etiological factor and pathogenesis is Yin Deficiency , especially the Deficiency of Kidney Yin. The treatment is Nourishing Yin to tonify Kidney. ecliptae herba is the important medicine to tonify Liver and Kidney. ecliptae herba is also the important medicine to treat diabetes in the differentiation of TCM. A lot of clinic and experiment research show that ecliptae herba has the active fuction to control diabetes and its complications, especially Diabetic NephropathyPurpose:Research the mech of the effect of ecliptae herba and the ralations of it accommodates the imbalance of base material of catabolic enzymes system. Method: The decreasing of the degrade rate of substrate is associated with the inhibition of matrix metalloproteinase (MMP). We study the inhibitory activity of ecliptae herba to MMP by observing the degrade rate of substrate. Result: ecliptae herba strongly inhibits the MMP-16 activity,according to the accentuation of the level,the inhibition fuction will strengthen, and the IC50 is 5.35μg/ml. Conclusion: ecliptae herba have the inhibitory activity to MMP-16,it is one of the mechs to treat the Diabetic Nephropathy .Matrix metalloproteinase is one member in zinc peptidase, it is an indispensable enzyme in composing connective tissue extracellular matrix degradation process. It can almost degradate all the compositions of extracellular matrix. The specific catastaltica of TIMP is a negative moderator to MMP in ECM's metabolic regulation. The system of MMP/TIMP has significant function in many physiological and pathological processes in vivo, its disharmony may mediate the occurrence of nephritis, tumor metastasis, artherosclerosis, multi-connective tissue diseases and important organs fibrous degeneration etc. Searching the new drugs as the curative target of MMP/TIMP is becoming of the hot spot in interior and exterrior exploitation. At present, several kinds of broad-spectrum and low molecular number of MMP's catastaltica are used in some kinds of tumor therapy are assessed in clinic. Altough these micromoecule medicines can high performance inhibit activity of MMP and prevent tumors'growth and diversion in preclinical animal experiments, their expensive price and fervent side effect in clinic lead to the failure in anaphase clinic. The reason is possibly because of their weak specificity. They influence many other kinds of the normal physiologic function of MMP in different extent. In the preliminary screening stage of this experiment, it was on the basis of the fourth edition of Chinese material medica textbook, random selects 38 kinds of herbs from tonic deficiency herb and adduct astringent herb. The result is there are 23 kinds of herbs has the function to inhibit matrix metalloproteinase, among these, ecliptae herba can have the inhibit function underμg grade. The pity is we cannot go a further step to observe its function with regard to TIMP and enzymatic system of MMP/TIMP through the extraorgan or animal experiment because of the limit time and constraint conditions. If to continue and consummate this experiment, it is hoped to educe sufficiently the superiority of the traditional Chinese medicine,by means of ecliptae herba as the represent which is got out of a new drug from the tonic and adduct astringent herb to treat the diseases which are related with the disharmony of matrix catabolic enzymes system, it can benefit humankind.