| Objective:Research the protective effects of Tongxinluo micronized powder combined Jinlida on DN and around the TGF-β1/Smad signal pathway, analyze the mechanism of DN.Methods:Healthy 80 male Sprague-Dawley (SD) rats were fed adaptively for 1 week and then randomly chose ten rats as Normal control group (N).The other 70 rats were maken modles. Rats in Normal control group were fed conventionally and the rats in the other 5 groups were fed with high-sucrose-fat diet during the experiment. Diabetes was induced after 4 weeks, all rats except that in N group were intravenous injected with STZ (35mg/kg) in tail, and the FBG were tested 72 hours later. Rats with FBG level higher than 11.1mmol/L were considered diabetic and were used for the study. Then, the DM models were divided to Model group (M), Irbesartan group (Ⅰ), Tonxinluo group (T), Jinlida group (J) and Tonxinluo combined Jinlida group (TCJ) according to the body weight. All the drugs were dissolved in 5‰ CMC solution to keep uniform suspension. Rats in M group were intragastric administrated with CMC for 10ml/kg/d, and I group with Irbesartan for 25mg/kg/d, T group with Tongxinluo for 0.8g/kg/d, J group with Jinlida for 1.5g/kg/d, TCJ group were combined with the previous two drugs together. The drug delivery lasted for 12 weeks. At the end of the twelth week, the left kidneys were weighed and conserved in 4% formaldehyde and 2.5% glutaraldehydefor pathomorphology observation and immunohistochemistry test, and the right kidneys were conserved in liquid nitrogen to detect the expression of smad2/3 and smad7 that in the TGF-β1/Smad signal pathway.Results:1 General state of healthAll the diabetic rats showed significant polydipsia, polyphagia, polyuria and emaciation.2 The expression of TGF-β1The expression of TGF-β1 was significantly enhanced in diabetic rats’ kidney, and the expression of TGF-β1 in administer groups was weakened by different degrees. Especially, in the TCJ group, the expression of TGF-β1 was similar with the N group.3 The expression of FN and CTGFThe expression of FN and CTGF was significantly enhanced in diabetic rats’kidney, and the expression of FN and CTGF in administer groups was weakened by different degrees. Especially, in the TCJ group, the expression of FN and CTGF was similar with the N group.4 The results of Western BlotTo compared with N group, the expression of Smad2/3 and p-Smad2/3 was significantly enhanced(P<0.01) in the model group, but the expression of Smad2/3was no difference (P≥0.05), at the same time, the expression of Smad7 decreased in the other groups but N group(P<0.05,P<0.01,)which means the activation of TGF-β1/Smad signal pathway. To compared with M group, the expression of Smad2/3 of I group and TCJ group was no difference (P≥0.05), but the expression of p-Smad2/3 was decreased than the M group(P<0.05); The expression of Smad7 was enhanced in I and TCJ group.The above showed that the TGF-β1/Smad signal pathway was conrolled in I and TCJ group.Conclusion:1 Tongxinluo micronized powder combined Jinlida has the function of reduce TGF-β1and Smad2/3. TGF-β1/Smad signaling pathway may be one of the mechanisms of shenxiao decoction effect for renal protection.2 Tongxinluo micronized powder combined Jinlida could suppress th the expression of FN、CTGF, which can reduction of extracellular matrix (ECM), reduce renal fibrosis, protect the kidney. |
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