| In this study, we have successfully established a mice model of diabetic nephropathy(DN). In order to explore the effects and possible mechanisms of Shenvan Extraction on DN, blood, urine biochemistry, renal histopathology and cytokines in transforming growth factor-β1 pathway are detected.DN model was induced by intraperitoneal injection of streptozotoc(STZ) (150mg/kg) in C57BL/6 mice. The change of the general situation, blood glucose, urine protein, kidney weight/body weight (KW/BW), blood urea nitrogen (BUN), serum creatinine (Scr) and pathomorphology in kidney by light microscopy and transmission electron microscopy in mice were observed. The results showed that compared with the normal control group, model group body weight of mice decreased significantly (P<0.01), from the third day blood glucose continued to rise(P<0.01), after 1 week proteinuria appeared and after 4 weeks BUN, Scr increased (P< 0.01). In the model group KW/BW was significantly higher(P<0.01), by light microscope glomerular hypertrophy, widened Essential area and matrix increase were observed, as well as glomerular sclerosis index was increased (P<0.05, P<0.01); by electron microscopy foot process broadening, flat, integration, reduction of foot cells and exposed glomerular basement membrane (GBM) were showed, and the GBM was significantly thicker (P<0.05, P<0.01).To explore the effects of Shen'an Extraction on DN mice blood sugar, urine protein, BUN and Scr. The C57BL/6 mice were randomly divided into normal control group, model group, irbesartan group, Shen'an low, middle and high-dose group. The intervention groups were respectively given the drug irbesartan 10mg/kg, mixture of Astragaloside, Icariin and 1,8-Dihydroxy anthraquinone(Shen'an Extraction) 2.272mg/kg,4.544mg/kg and 9.088mg/kg for 4 weeks by gavage. The results showed that the blood glucose in the other groups with persistent hyperglycemia, with no difference between them(P>0.05), is significantly higher than the normal control group(P<0.01). The urine protein in the drug intervention groups was significantly lower than the model group(P<0.01), and was no difference between Shen'an high-dose and irbesartan group (P>0.05). After 4 weeks, compared with the model group, the BUN in all drug intervention groups and Scr in Shen'an high-dose group and irbesartan group were significantly lower (P<0.05, P<0.01). The BUN in Shen'an high-dose group was lower than irbesartan group(P <0.05); Scr was no difference between them(P>0.05).In the histological study of kidney, tissue samples are based on the biochemistry research components, grouped with the same way. The results showed that in each dose group with Shen'an Extraction KW/BW, glomerular sclerosis index, FN expression and GBM thickness were all significantly improved(P<0.05, P<0.01). FN expression was no difference between Shen'an high-dose group and irbesartan group (P>0.05), and the other indexes were no difference between Shen'an middle/high-dose group and irbesartan group (P>0.05), too. As the dose increased Shen'an Extraction, renal pathological was thus gradually alleviated.In this study, DN mice kidney transcription activator protein-1(AP-1) (western blot), TGF-β1 mRNA(RT-PCR) and protein (Immunohistochemistry) was detected. The results showed that protein expression of AP-1 (c-Jun subunit) of kidney in each dose group with Shen'an Extraction was significantly lower than model group(P<0.01), and no difference between Shen'an high-dose group and irbesartan group(P>0.05); mRNA and protein expression of TGF-β1 of kidney in each dose group with Shen'an Extraction were significantly lower than model group(P<0.01), and no difference between Shen'an high-dose group and irbesartan group(P>0.05).In the last part DN mice kidney p38 mitogen activated protein kinase(MAPK) mRNA (RT-PCR), phosphor-p38MAPK(p-p38MAPK) and Smad7 (Immunohistochemistry) expression was detected. The results showed that mRNA expression of p38MAPK of kidney in each dose group with Shen'an Extraction was significantly lower than model group(P< 0.01), and no difference between Shen'an high-dose group and irbesartan group(P>0.05); protein expression of p-p38MAPK and Smad7 of kidney in each dose group with Shen'an Extraction were significantly lower than model group(P<0.01), and no difference between Shen'an high-dose group and irbesartan group (P>0.05).In conclusion, Shen'an Extraction can reduce urinary protein, improve renal function, ameliorate renal pathological changes, delay the onset of glomerular sclerosis, and renal damage is protected in DN mice. The mechanism may be related to reduce the accumulation of ECM and inhibit foot cell apoptosis by reducing renal AP-1 protein expression, thereby inhibiting TGF-β1 expression and signal transduction.
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