| Objective: Focal Segmental Glomerulosclerosis (FSGS) is a common non-inflammation sclerosis pathological change involved in the capillary and glomeruli , which is a common pathologic process of most kidney disease leading to renal failure. The pathological character shows that messegium increased, transparency material of the glomerulus basement membrane epithelium accumulates, capillary and capsular adheres. FSGS is the main pathologic type of nephropathy, which leads to end-stage renal failure 10 years after discovered, and induces glomerulosclerosis and interstitial fibrosis. Most FSG patients with nephritic syndrome react weakly to steroid and the cytotoxic drug treatment, with heavy side effect. Angiotensin converting enzyme inhibitor (ACEI) and Angiotensin II receptor blocker (ARB) can protect the renal function, but the treatment of ACEI and ARB is only one way to kidney disease caused by different pathogenesis. Furthermore, ACEI and ARB have invariably renal damage. So looking for safe drugs is of great significance. Various clinical studies has confirmed that the FSGS has something to do with blood clotting and dissolving system obstacle. Unbalance of blood coagulation and hemolysis system is the important pathophysiologic changes in glomerulosclerosis and interstitial fibrosis. The system depends on Plasminogen activator (t-PA) and Plasminogen antivator inhibition (PAI-1) to adjustment. The key enzyme in the blood coagulation process — zymoplasm, can promote the inherent cell proliferation and secrete various growth factors and the expression of the cell factor, among them including PAI-1 etc., and downregulated the express of t-PA . The research shows that the t-PA is one of the protection factors of the kidney. PAI-1, a specific inhibition factor of t-PA, not only represses in the plasminogen conversion to fibrinolysin so as to inhibit fibrious hydrolysis, but also inhibits extracellular matrix (ECM) accumulation. The plasmase zymoplasm can make fibre proteinosis and inhibit matrix degradation through the up-regulation of PAI-1, lead to glomerulosclerosis. It is important to regulate the balance of blood coagulation and hemolysis system in treatment. It is believed that glomerulosclerosis and ECM accumulation, glomeruli and capsular adhesion, the microthrombus, capillary luman collapse or narrow, interstitial fibrosis with atrophy etc. all of the pathology changes are the category of the stagnant blood internal resistance. So the method of activating blood circulation to dissipate blood stasis must be used. Hong Hua, a Chinese herbal medicine, with the role to activate blood circulation to dissipate blood stasis, has the anticogulation function, keeping blood from bolting formation which is already extensive applied in the type of the cardiovascular and cerebrovascular disease. There is no report about the effect of Hong Hua on blood blood coagulation and hemolysis system and pathomorphology in renal disease. Hong Hua was used in this experiment to treat the FSGS rats model induced by Adriamycin , to observe the expressions of t- PA and its inhibitor PAI-1 with immunohistochemistry and mRNA PAI-1 with in situ hybridization, combining with the renal histochemistry observation, meanwhile the mechanism of Hong Hua in kidney disease was discussed compared to Valsartan.Method: Forty male Sprague-Dawley rats were put into metabolism cage to obtain urine, and urine protein and red blood cell were detected. The result was negative. Then they were randomly divided into four groups (n=10), Sham-operation, Model, Valsartan, Hong Hua. Each animal adopted right side nephrectomy, tail intravenous injection of 0.1% A driamycin respectively after 7 and 30 days of operation except Sham group. Drugs were administered from seventh day after operation but the saline were used in Sham and Model groups orally. Animals were sacrificed after 8 weeks, proceeded by the routine and biochemistry check, and the left side was obtained for pathology observing, expressions of t-PA and PAI-1 were detected by... |
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