丹参酮ⅡA磺酸钠注射液对心肌缺血再灌注大鼠心功能和免疫反应的调节作用
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摘要
目的本文研究丹参酮ⅡA磺酸钠注射液(Sodium tanshinone ⅡA sulfonate,TⅡA)对心肌缺血再灌注(ischemia-reperfusion,I/R)大鼠心功能和免疫反应的调节作用及其机制。方法采用冠状动脉结扎法建立心肌缺血再灌注大鼠模型;随机分成5组:Ctrl组、I/R组、I/R+TⅡA(0.5 mL)组、I/R+TⅡA(1mL)组和I/R+TⅡA(2 mL)组;测定平均动脉压(mean ventricular systolic pressure,MAP)、左室收缩压(left ventricular systolic pressure,LVSP)和心率(heart rate,HR);采集血清Elisa检测心损标记物表达水平和氧化应激指标含量;HE染色和TUNEL染色观察心肌损伤情况;流式分选外周血CD4+iNOS+,CD4+IL-10+凋亡变化;蛋白印迹法检测凋亡相关蛋白和P65、IL-8及TNF-α表达情况。结果丹参酮ⅡA磺酸钠注射液能上调MAP、HR和LVSP水平以改善I/R模型大鼠心功能(P<0.01);降低血清中CK-MB、cTnΙ和Mb的表达上调;减少MDA、LDH表达,增加SOD水平;改善心肌组织的病理改变,抑制心肌细胞凋亡,上调Bcl-2、下调Bax蛋白表达(P<0.01);减少iNOS+和增加IL-10~+细胞凋亡而改善Th1/Th2平衡(P<0.01);抑制P-P65、IL-8和TNF-α的表达下调(P<0.01)。结论丹参酮ⅡA磺酸钠注射液对心肌缺血再灌注损伤具有保护作用,其机制与改善心功能,调节免疫反应有关。
Objective To investigate the effects of sodium tanshinone IIA sulfonate on cardiac function and immune response in rats with myocardial ischemia-reperfusion(I/R) injury and its mechanism.Methods The model of myocardial ischemia-reperfusion was established by coronary artery ligation. The rats were randomly divided into five groups: Ctrl group, I/R group, I/R + TIIA(0.5 mL), I/R + TIIA(1 mL)group and I/R + TIIA(2 mL) group. The mean ventricular systolic pressure(MAP), left ventricular systolic pressure(LV) and heart rate(HR) were measured. The expression of heart damage markers and the content of oxidative stress indicators were detected by Elisa test. HE staining and TUNEL staining were used to evaluate myocardial injury. The changes of CD4+iNOS+and CD4+IL-10+apoptosis in peripheral blood were evaluated by flow cytometry. Western blotting was used to detect the expression of apoptosis-related proteins and P65,IL-8 and TNF-α. Results Sodium tanshinone II A sulfonate injection could up-regulate the levels of MAP,HR and LVSP to improve the cardiac function of I/R model rats(P<0.01), reduce the expression of CK-MB,cTnΙ and MB in serum, and reduce the expression of MDA and LDH while increase SOD, improve the pathological changes of myocardial tissue, inhibit myocardial apoptosis, and up-regulate Bcl-2 and downregulate the Bax(P<0.01), decrease apoptosis of iNOS+and increase IL-10~+ in order to improve Th1/Th2 balance(P<0.01), inhibit the down-regulation of P-P65, IL-8 and TNF-α expression induced by I/R injury(P<0.01). Conclusions Sodium tanshinone IIA sulfonate injection has protective effect on myocardial ischemia-reperfusion injury which is related to improving cardiac function and regulating immune response.
Objective To investigate the effects of sodium tanshinone IIA sulfonate on cardiac function and immune response in rats with myocardial ischemia-reperfusion(I/R) injury and its mechanism.Methods The model of myocardial ischemia-reperfusion was established by coronary artery ligation. The rats were randomly divided into five groups: Ctrl group, I/R group, I/R + TIIA(0.5 mL), I/R + TIIA(1 mL)group and I/R + TIIA(2 mL) group. The mean ventricular systolic pressure(MAP), left ventricular systolic pressure(LV) and heart rate(HR) were measured. The expression of heart damage markers and the content of oxidative stress indicators were detected by Elisa test. HE staining and TUNEL staining were used to evaluate myocardial injury. The changes of CD4+iNOS+and CD4+IL-10+apoptosis in peripheral blood were evaluated by flow cytometry. Western blotting was used to detect the expression of apoptosis-related proteins and P65,IL-8 and TNF-α. Results Sodium tanshinone II A sulfonate injection could up-regulate the levels of MAP,HR and LVSP to improve the cardiac function of I/R model rats(P<0.01), reduce the expression of CK-MB,cTnΙ and MB in serum, and reduce the expression of MDA and LDH while increase SOD, improve the pathological changes of myocardial tissue, inhibit myocardial apoptosis, and up-regulate Bcl-2 and downregulate the Bax(P<0.01), decrease apoptosis of iNOS+and increase IL-10~+ in order to improve Th1/Th2 balance(P<0.01), inhibit the down-regulation of P-P65, IL-8 and TNF-α expression induced by I/R injury(P<0.01). Conclusions Sodium tanshinone IIA sulfonate injection has protective effect on myocardial ischemia-reperfusion injury which is related to improving cardiac function and regulating immune response.
引文
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[2]Zhang N,Wang LR,Li DD,et al.Interferon-αcombined with herbal compound"songyou yin"effectively inhibits the increased invasiveness and metastasis by insufficient radiofrequency ablation of hepatocellular carcinoma in an animal model[J].Integr Cancer Ther,2018,17(4):1260-1269.
[3]Zhong C,Zhang YF,Huang JH,et al.The chinese medicine,Jianpi Huayu Decoction,inhibits the epithelial mesenchymal transition via the regulation of the Smad3/Smad7 cascade[J].Am J Transl Res,2017,9(6):2694-2711.
[4]Yuan FY,Zhang M,Xu P,et al.Tanshinone IIA improves diabetes mellitus via the NF-κB-induced AMPK signal pathway[J].Exp Ther Med,2018,16(5):4225-4231.
[5]Dong W,Zhang Y,Chen X,et al.High-Dose tanshinone IIA suppresses migration and proliferation while promoting apoptosis of astrocytoma cells via notch-1 pathway[J].Neurochem Res,2018,43(9):1855-1861.
[6]Deng L,Chen H,Wei N,et al.The cardioprotective effect of dexmedetomidine on regional ischemia/reperfusion injury in type 2diabetic rat hearts[J].Microvasc Res,2019,123:1-6.
[7]Yang L,Zhang Y,Zhu M,et al.Resveratrol attenuates myocardial ischemia/reperfusion injury through up-regulation of vascular endothelial growth factor B[J].Free Radic Biol Med,2016,101:1-9.
[8]Feng J,Li S,Chen H.Tanshinone IIA inhibits myocardial remodeling induced by pressure overload via suppressing oxidative stress and inflammation:possible role of silent information regulator 1[J].Eur JPharmacol,2016,791:632-639.
[9]Seedevi P,Moovendhan M,Viramani S,et al.Bioactive potential and structural characterization of sulfated polysaccharide from seaweed(Gracilaria corticata)[J].Carbohydr Polym,2017,155:516-524.
[10]Ren X,Wang C,Xie B,et al.Tanshinone IIA induced cell death via miR30b-p53-PTPN11/SHP2 signaling pathway in human hepatocellular carcinoma cells[J].Eur J Pharmacol,2017,796:233-241.
[11]Ma X,Chen S,Jin W,et al.Th1/Th2 PB balance and CD200 expression of patients with active severe alopecia areata[J].Exp Ther Med,2017,13(6):2883-2887.
[12]Shu M,Hu XR,Hung ZA,et al.Effects of tanshinone IIA on fibrosis in a rat model of cirrhosis through heme oxygenase-1,inflammation,oxidative stress and apoptosis[J].Mol Med Rep,2016,13(4):3036-3042.