虎杖对脂多糖诱导大鼠急性肺损伤的治疗作用

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目的探讨虎杖(polygonum cuspidatum,PC)煎剂对脂多糖(LPS)诱导Wistar大鼠急性肺损伤(ALI)的治疗作用,并探讨其可能机制和临床意义。方法给大鼠静注LPS复制ALI动物模型。首先动态观察ALI的形成过程,给予LPS后2 h已形成明显的ALI(病理切片证实)。随机将72只Wistar大鼠分成4组,每组18只。对照组(静注生理盐水1 ml/kg体重),LPS组(静注LPS,5 mg/kg体重),PC组(正常大鼠每天PC煎剂灌胃,5 ml.次-1.只-1,1次/d,共7 d);PC治疗组(给予LPS 2 h后开始灌胃,灌注PC煎剂5 ml.次-1.只-1,1次/d,共7 d)。每组大鼠分别于2、48 h和7 d三个时间点各处死6只,按时相观察和收集样本,进行测定和病理切片检查。测定肺系数、肺湿重/肺干重(W/D)、肺含水率,光镜观测肺组织病理变化,检测在实验性ALI大鼠肿瘤坏死因子-α(TNF-α)、白介素-6(IL-6)、血栓素B2(TXB2)、髓过氧化物酶(MPO)等细胞因子、炎性介质的表达。各组大鼠动脉血气分析比较。结果给予LPS后肺W/D和血清TNF-α、IL-6、TXB2含量及肺组织MPO活性显著高于对照组(P<0.05,P<0.01)。而给予PC煎剂可显著缓解上述变化(P<0.01)。LPS组氧分压(PaO2)较对照组显著降低,二氧化碳分压(PaCO2)显著升高(均P<0.01);PC治疗组PaO2显著高于LPS组(P<0.05),PaCO2显著低于LPS组(P<0.05)。PC组与对照组差异不显著。结论静注LPS(5 mg/kg)可成功复制ALI动物模型。ALI的发生和发展与血清TNF-α、IL-6、TXB2等炎性因子有密切关系。PC通过降低上述炎症因子释放减轻病理损伤在治疗ALI中有一定应用前景。 Objective To investigate the therapeutic effect of Polygonum cuspidatum (PC) decoction on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in Wistar rats, and to explore its possible mechanism and clinical significance. METHODS: Rats were treated with intravenous LPS to replicate ALI animal models. First of all, dynamic observation of the formation of ALI, 2h after LPS has been formed significantly ALI (pathological section confirmed). 72 Wistar rats were randomly divided into 4 groups, 18 in each group. Control group (intravenous saline 1 ml/kg body weight), LPS group (intravenous LPS, 5 mg/kg body weight), PC group (normal rats daily PC decoction, 5 ml. times -1. only - 1,1 times/d for a total of 7 days); PC treatment group (2 hours after LPS administration, gastric perfusion was started, perfusion with PC decoction 5 ml, time -1. only -1, 1 time per day for 7 days). Six rats in each group were sacrificed at 2, 4, and 7 days respectively. The samples were observed and collected at different time points for measurement and pathological examination. The lung coefficient, lung wet weight/lung dry weight (W/D) and lung water content were measured. Lung pathological changes were observed by light microscopy. Tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 were detected in experimental ALI rats. Expression of cytokines (IL-6), thromboxane B2 (TXB2), myeloperoxidase (MPO), and inflammatory mediators. Arterial blood gas analysis in each group was compared. Results After administration of LPS, lung W/D and serum TNF-α, IL-6, TXB2 levels and lung MPO activity were significantly higher than those in the control group (P<0.05, P<0.01). The administration of PC decoction significantly alleviated the above changes (P<0.01). Oxygen partial pressure (PaO2) in LPS group was significantly lower than that in control group, and PaCO2 was significantly increased (all P<0.01); PaO2 in PC group was significantly higher than that in LPS group (P<0.05), and PaCO2 was significantly lower than LPS. Group (P < 0.05). There was no significant difference between the PC group and the control group. Conclusions Intravenous LPS (5 mg/kg) can successfully replicate ALI animal models. The occurrence and development of ALI are closely related to serum TNF-α, IL-6, TXB2 and other inflammatory factors. PC reduces the release of the above-mentioned inflammatory factors to reduce pathological damage in the treatment of ALI has a certain application prospects.
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