| ObjectiveObserve the effects and probe into the mechanism of Mangiferin on myocardial apoptosis in DCM rats induced by streptozotocin. Investigate the basic foundation of JNK signal transduction mediated by IRE1α, related with ERS protein.MethodsThe 50 Sprague-Dawley(SD) male rats were randomly selected 40 rats for offering tail intravenous injection of streptozotocin with 45mg/kg after fasting for12 hours. The blood glucose of rats equal or greater than 16.7 mmol/L were established diabetic model. The remaining 10 rats were injected with citric acid buffer solution. The DM rats were randomly divided into 4 groups: the diabetic model group(STZ), Mangiferin low group(STZ+M-L, 15 mg/kg·d), Mangiferin medium group(STZ+M-M, 30 mg/kg·d), Mangiferin high group(STZ+M-H, 60mg/kg·d), and each group was given intragastric administration for 12 weeks.After 12 weeks: rats were respectively measured fasting blood glucose;Observe the morphologic alternation of myocardial tissue by HE staining;Survey the variety of hemodynamics; Test The rate of myocardial apoptosis by TUNEL;Detect the protein expressions of p-IRE1α, ASK1 and p-JNK through immunohistochemistry and Western blot.ResultsCompared with the control group, fasting blood glucose [(24.58±2.30)mmol/L] of the diabetic rats was significantly up-regulated(P<0.01); myocardial tissues were damaged obviously through morphology; index of hemodynamics were altered remarkably(P<0.01), heart function was declined significantly; the apoptosis rate(11.75 ± 1.41)% of myocardial cells increased obviously(P<0.01); protein expressions of p-IRE1α and p-JNK showed strongly positive,and the cytoplasm was wide-bound tintaged; protein expression of ASK1 indicated obviously positive, and large brown grannles deposited in the cytoplasm. Compared with STZ group, index of Mangiferin treatment groups were improved, and STZ+M-H group was improved obviously(P <0.01). Fasting blood glucose [(15.38±1.34)mmol/L] of STZ+M-H group declined significantly(P<0.01); morphologic and hemodynamics index improved remarkably; the apoptosis rate [(5.22 ±1.71)%] of the myocardial cells decreased significantly(P<0.01); protein expressions of p-IRE1α and p-JNK declined obviously(P<0.01), and cytoplasm was mid-range tintaged; protein expressions of ASK1 declined remarkably(P<0.01), the brown grannles deposited in cytoplasm were decreased.ConclusionMangiferin can inhibit the myocardial cell apoptosis of diabetic rats and it may be related to the reductions of blood glucose and inhibitions of JNK signal transduction mediated by IRE-1α. |
