目的 探討白芍總苷（total glucosides of paeony，TGP）對糖尿病大鼠心肌氧化應激和細胞凋亡的影響及其機制。方法 取120只SD大鼠按隨機數(shù)字表法分為對照組、模型組、二甲雙胍（Met，200 mg/kg）組和TGP低、中、高劑量（50、100、200 mg/kg）組，每組20只；采用一次性ip鏈脲佐菌素（65 mg/kg）制備糖尿病大鼠模型；造模后連續(xù)8周每天1次ig給藥，對照組和模型組同步ig給予生理鹽水。通過血糖儀檢測空腹血糖水平；生化分析法檢測血清乳酸脫氫酶（LDH）、肌酸激酶同工酶（CK-MB）、丙氨酸氨基轉(zhuǎn)移酶（ALT）含量和心肌組織丙二醛（MDA）含量、抗氧化酶——超氧化物歧化酶（SOD）、谷胱甘肽過氧化物酶（GSH-Px）活性；通過HE染色、TUNEL染色觀察心肌病理學改變和細胞凋亡；Western blotting法檢測心肌組織GRP78、CHOP、Cleved Caspase-12蛋白表達。結(jié)果 與模型組比較，Met組和TGP中、高劑量組大鼠空腹血糖水平顯著降低，血清LDH、CK-MB、ALT水平和心肌組織MDA含量顯著降低，心肌組織SOD、GSH-Px活性顯著升高，心肌組織病理損傷和細胞凋亡狀況明顯改善、凋亡指數(shù)（AI）顯著降低，心肌組織GRP78、CHOP、Cleved Caspase-12蛋白表達顯著下調(diào)，差異有統(tǒng)計學意義（P<0.05、0.01）。結(jié)論 TGP對糖尿病大鼠心肌氧化應激和細胞凋亡具有抑制作用，其機制可能與提高抗氧化酶活性和抑制內(nèi)質(zhì)網(wǎng)應激凋亡通路有關。

Objective To investigate the effect of total glucosides of paeony (TGP) on myocardial oxidative stress and apoptosis in diabetic rats and its mechanism. Methods Tatolly 120 SD rats were randomly divided into control group, model group, metformin group (70 mg/kg) and TGP low-, mediumand high-dose groups (50, 100 and 200 mg/kg). The diabetic rat models were prepared by ip injection of streptozotocin (65 mg/kg). After the model was established, the drugs were given by gavage simultaneously, once a day for eight weeks, while the rats in the control group and model group were given normal saline. The fasting blood glucose level was detected by blood glucose meter, the content of LDH, CK-MB, ALT in serum and the content of MDA, the activity of ntioxidant enzyme (SOD, GSH-Px) in myocardial were etected by biochemical analysis; The pathological changes and apoptosis of myocardium were observed by HE staining and TUNEL staining; The expression of GRP78, CHOP, Cleved Caspase-12 protein in myocardial tissue was detected by Western blotting method. Results Compared with model group, the fasting blood glucose levels of rats in metformin group and TGP medium-, high-dose groups were significantly decreased; the content of LDH, CK-MB, ALT in serum and MDA in myocardial were significantly decreased, and the activity of SOD, GSH-Px in myocardial were significantly increased; the pathological damage and apoptosis of myocardial tissue were significantly improved, the AI was significantly decreased; the expression of GRP78, CHOP, Cleved Caspase-12 were significantly down-regulated; the differences were significant (P<0.05 or 0.01). Conclusion TGP has inhibitory effect on myocardial oxidative stress and apoptosis in diabetic rats, and its mechanism may be related to increasing antioxidant enzyme activity and inhibiting endoplasmic reticulum stress apoptosis pathway.

R285.5

邯鄲市科學技術研究與發(fā)展計劃項目（1823208094ZC）