益气活血通络解毒方对小鼠肺缺血/再灌注损伤的作用及其机制

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目的:探讨益气活血通络解毒方(YHTJF)对小鼠的肺部缺血/再灌注(I/R)损伤,及对I/R引起的氧化应激反应的作用。方法:成年雄性10~12周龄C57BL/6J小鼠70只,体重(21~25)g,采用在体左肺门夹闭法复制缺血/再灌注损伤模型。随机分为7组:正常对照组(C),羧甲基纤维素钠carboxyl methyl cellulose-Na(CMC-Na)+正常对照组(CC),羧甲基纤维素钠+假手术组(CS),羧甲基纤维素钠+I/R模型组(CIR),羧甲基纤维素钠+YHTJF低、中、高浓度干预组(CYL、CYM、CYH)。CN、CS、CIR组术前连续7 d腹腔注射CMC溶液,CYL、CYM、CYH组术前连续7 d腹腔注射低、中、高浓度的YHTJF溶液。术毕,取左肺测定肺组织干湿比(W/D)及总肺含水量(TLW),行肺组织损伤评估(IQA),光镜观察肺组织形态学结构改变。TUNEL测组织细胞凋亡指数(AI)。检测血清超氧化物歧化酶(SOD)、丙二醛(MDA)、髓过氧化物酶(MPO)。结果:相比C组,CC组和CS组所有检测指标均无明显差异,CIR组的W/D、TLW、IQA、AI明显升高(P<0.01),肺组织形态学破坏显著;MDA含量、MPO活力明显升高,SOD活性显著降低。与CIR组比较,CYL组、CYM组、CYH组W/D、TLW、IQA、AI的表达均明显下降(P<0.01),组织损伤明显减轻,CYM组各项指标数值改善最明显,组织损伤最轻;3个用药组的MDA含量、MPO活力明显下降,SOD活性显著升高,其中中剂量用药组氧化应激指标变化最突出。结论:YHTJF可有效减轻小鼠缺血/再灌注性肺损伤,以中剂量效果为最佳,其机制可能与其抑制体内氧化应激反应、减轻肺组织细胞凋亡有关。 Objective: To investigate the effects of YHTJF on lung ischemia / reperfusion (I / R) injury and oxidative stress induced by I / R in mice. Methods: Seventy male C57BL / 6J mice aged 10-12 weeks old weighing 21-21 g were used in the model of ischemia / reperfusion injury in vivo. The rats were randomly divided into 7 groups: normal control group (C), sodium carboxymethylcellulose CMC (CMC-Na) + normal control group (CC), sodium carboxymethylcellulose + sham operation group (CS) , Sodium carboxymethylcellulose + I / R model group (CIR), sodium carboxymethylcellulose + YHTJF low, medium and high concentration intervention group (CYL, CYM, CYH). The rats in CN, CS and CIR groups were given intraperitoneal injection of CMC solution for 7 consecutive days. The low, middle and high concentrations of YHTJF solution were intraperitoneally injected into the CYL, CYM and CYH groups for 7 consecutive days. At the end of operation, the left lung was taken to determine the wet / dry ratio (W / D) and the total lung water content (TLW) of the lungs, and the lung injury assessment (IQA) was performed. TUNEL measured apoptosis index (AI). Serum superoxide dismutase (SOD), malondialdehyde (MDA) and myeloperoxidase (MPO) were detected. Results: Compared with group C, there was no significant difference between CC group and CS group. The W / D, TLW, IQA and AI in CIR group were significantly increased (P <0.01) , MPO activity was significantly increased, SOD activity was significantly reduced. Compared with CIR group, the expression of W / D, TLW, IQA and AI in CYL group, CYM group and CYH group were significantly decreased (P <0.01), the tissue damage was significantly reduced, the index of CYM group was the most obvious improvement, tissue damage Lightest; MDA content, MPO activity of three treatment groups decreased significantly, SOD activity increased significantly, of which the dose-dependent changes in the most prominent indicators of oxidative stress. Conclusion: YHTJF can effectively reduce the ischemia / reperfusion lung injury in mice, with the best dose effect, which may be related to its inhibition of oxidative stress in vivo and alleviation of lung cell apoptosis.
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