| Diabetic nephropathy (DN), a most common and seriously chronic complication of diabetes mellitus (DM), has been the mainly reason to cause mortality rate and mutilation rate increasing in diabetic patients at present. Diabetic nephropathy is realized as a glomerular sclerosis mainly characterized by the hypertrophy of both glomerular and tubular elements,diffuse thickness of glomerular basement membrane(GBM), and increased synthesis of extra cellular matrix (ECM) in the mesangial region and interstitium. The pathogenesis of DN is a synthetic result initiated by sustained hyperglycemia as initiating element and multiple factors including glyeolipid metabolism disorder, hemodynamic changes, and cell cytokines are involved in.But because renal lesions are concealed, diagnostic markers are deficiency, DN can not be found in the early stage usually.While clinical symptoms occurr significantly, urinary protein is positive continually,pathological changes have progress to an irreversible stage. The modern medicine still has no specific treatment to prevent and cure it by now. Therefore, how to diagnosis and cure the DN effectively in early phase is signality for preventing DN development.Measuring the change of urinary micro albumin(UMA)is the primary examination and diagnosis technique of early DN at present, that test facility is too insensitive to diagnose and discover early DN,especially DN inâ… ~â…¡phase effectively. Puncture percutaneous renal biopsy is another major diagnostic method of DN, which has a high accuracy ,but it's very difficult to popularize and apply such a hurtful method at clinic universality. Therefore, to explore an early diagnosis means for DN which has higher susceptiveness, veracity and to carry on effectual interventions as soon as possible are imperative under the situation. We hope some specific metabolic markers of DN could be found to inrease early DN diagnosis rate through analyzing DN(â…¡phase) rats'urinary metabolites by using high performance liquid chromatography technique (HPLC) .Comparing by symptoms,DN is just similar to those complication of consumptive thirst (XiaoKe disease), such as kidney consumption, oedema disease,turbid urine, urinary blockage and consumptive diseases in the category of TCM. Its Pathogenesis is that asthenia accompanied with sthenia becomes a reciprocal causation, is dominated by deficiency of both qi and yin, obstruction of collaterals by blood stasis in early stage. So we follow the TCM principle of treatment on syndrome differentiation,establish the therapeutic method of supplementing Qi and activating blood circulation, seeking both temporary and permanent solutions, and choice self-prescribed SanQi decoction to research its intervention effects in the early DN rat.Objective: This is a preliminary research in uric metabolic products biomarkers and treatment mechanism of self-prescribed SanQi decoction using in early DN period(â…¡phase). This project analyzes uric metabolic fingerprint of DN (â…¡phase) rats mainly by means of HPLC, to establish objective early diagnosis standard of DN, and to explore the curative effect and inherent mechanism of self-prescribed SanQi decoction from point of view of urine metabonomics. Meanwhile, we will identify chemical constitution and denotation of uric metabolic products, to search DN uric metabolic marker and to establish groundwork of early DN diagnosis standard in the future.Methods:The DN(â…¡p hase) rats model is induced by excision of the right kidney and a trial time intraperitoneal injection of streptozotocin (STZ). 40 male Wistar rats were divided randomly into 3 groups:SanQi group (feed self-prescribed SanQi decoction once a day by gastric tube), nephrotic model group, and sham-operated group (feed an equal volume of distilled water). At the end of the 8th week, we observe the rats general status, measure blood glucose, 24h urinary micro-albumin, renal function, and detect the pathomorphological change of kidney (through HE, PAS, EM). HPLC method was used to detect the uric metabolic fingerprint of the rats in order to discover pathologic metabolite in rats'urine and the interventional effects of self-prescribed SanQi decoction.Results:1. Self-prescribed SanQi decoction could improve the general status of the DN(â…¡phase) rats obviously(P<0.01), increase their body weight significantly ( P<0.01 ) , and decrease their kidney hypertrophy index significantly(P<0.01).2. Self-prescribed SanQi decoction could depress the level of their blood glucose significantly(P<0.01).3. Self-prescribed SanQi decoction could improve their renal function (BUN,Cr) significantly(P<0.01), but couldn't influence 24h urine volume obviously(P>0.05).4. Self-prescribed SanQi decoction could cure their pathologic lesion of renal glomerulus cell obviously.5. Compared with sham-operated groups, not only Area(A1,A2,A1/A2)of HPLC uric metabolic fingerprints of the rats on the 15min and 20min ,but also height(H1,H2,H1/H2)have changed significantly(P<0.01), self-prescribed SanQi decoction have intervention effects on above indexes of the rats, but couldn't influence them obviously(P>0.05).Conclusion:1. Uric metabolic products component has changed so apparently in the early DN (â…¡phase), that we can diagnose DN in very early period by detecting uric metabolites changes. The result of this empirical study indicates that two main metabolic products have changed obviously in composition. These two metabolic products may be specific markers of DN. The chemical constitution and denotation of them need further research to identify.2.Chinese prescription of self-prescribed SanQi decoction, that can supplement Qi and activate blood circulation exists the intervention effects on urine metabolic components of DN(â…¡phase) rats. These effects prove that self-prescribed SanQi decoction could cure early DN. The pharmacodynamics result shows that self-prescribed SanQi decoction could depress blood glucose and protect renal function significantly. But the urine metabonomics result shows that intervention of self-prescribed SanQi decoction on urine metabolic component of DN(â…¡phase) rats has not reached the obvious effect yet. Its reason may be concerned with short feed time and low feed dosage.
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