微创医学

目的研究川牛膝醇提物对野百合碱（MCT）诱导的大鼠肺动脉高压的影响及其相关机制。方法将40只SD大鼠随机均分为5组：对照组、MCT组、高剂量组（川牛膝醇提物24 g/kg）、中剂量组（川牛膝醇提物12 g/kg）和低剂量组（川牛膝醇提物6 g/kg）。后4组大鼠均一次性腹腔注射MCT 60 mg/kg建立肺动脉高压模型，对照组注射等量生理盐水。MCT注射第28天，高、中、低剂量组分别给予相应剂量的川牛膝醇提物灌胃。6周后，测量各组大鼠平均肺动脉压（mPAP）和右室收缩压（RVSP），检测血清丙二醛（MDA）含量和超氧化物歧化酶（SOD）的活性，苏木素-伊红（HE）染色法观察并计算肺小动脉血管壁厚度（WT）百分比，称重法计算右心室肥厚指数，采用Westem blot、逆转录聚合酶链反应（RTPCR）法分别观察大鼠肺组织磷酸肌醇-3-激酶（PI3K）、蛋白激酶B （Akt）蛋白及其mRNA的表达。结果与对照组结果比较，MCT组和低剂量组mPAP、RVSP、右心室肥厚指数、WT百分比明显升高（P＜0.05），PI3K、Akt蛋白及其mRNA表达水平明显升高（P＜0.05）。与MCT组结果比较，高、中剂量组mPAP、RVSP、右心室肥厚指数、WT百分比明显降低（P＜0.05），PI3K、Akt蛋白及其mRNA表达水平明显降低（P＜0.05）。高、中剂量组与对照组比较，mPAP、RVSP、右心室肥厚指数、WT百分比差异无统计学意义（P＞0.05），PI3K、Akt蛋白及其mRNA表达水平差异无统计学意义（P＞0.05）。高、中、低剂量组SOD活性明显高于对照组，MDA含量明显低于对照组（P＜0.05）。结论川牛膝醇提物可以降低野百合碱诱导的肺动脉高压，抑制氧化应激反应，降低肺血管重构，其机制可能与下调肺组织PI3K/Akt信号通路有关。

ObjectiveTo investigate the effect of ethanol extract of Cyathula officinalis Kuan on monocrotaline（MCT）-induced pulmonary hypertension in rats and its related mechanism. MethodsForty SD rats were randomly divided into five groups: control group, MCT group, high dose group (24g/kg ethanol extract of Cyathula officinalis Kuan), medium dose group (12 g/kg ethanol extract of Cyathula officinalis Kuan) and low dose group (6g/kg ethanol extract of Cyathula officinalis Kuan). Pulmonary hypertension model was established by one-time intraperitoneal injection of 60mg/kg MCT in the latter four groups, and the injection of equivalent volume of normal saline was performed in the control group. On the 28th day after MCT injection, the high, medium and low dose groups were given corresponding doses of ethanol extract of Cyathula officinalis Kuan by gavage separately. Six weeks later, mean pulmonary artery pressure (mPAP) and right ventricular systolic pressure (RVSP) were measured in each group, serum malondialdehyde(MDA) content and superoxide dismutase (SOD) activity were detected, the percentage of wall thickness (WT) of pulmonary arterioles was observed by hematoxylin-eosin (HE) staining and then calculated, right ventricular hypertrophy index was calculated by weighing method, the expression of phosphoinositide-3 kinase (PI3K) protein, PI3K mRNA, protein kinase B (Akt) protein and Akt mRNA in rat lung tissue was observed by Western blot and reverse transcription polymerase chain reaction, respectively. ResultsCompared with the control group, the MCT group and the low dose group had significantly higher mPAP, RVSP, right ventricular hypertrophy index and WT percentage as well as significantly higher expression levels of PI3K protein, PI3K mRNA, Akt protein and Akt mRNA (P＜0.05). Compared with the MCT group, the high and medium dose groups had significantly lower mPAP, RVSP, right ventricular hypertrophy index and WT percentage as well as significantly lower expression levels of PI3K protein, PI3K mRNA, Akt protein and Akt mRNA (P＜0.05). There was no statistically significant difference in mPAP, RVSP, right ventricular hypertrophy index or WT percentage between the high or medium dose group and the control group (P＞0.05), and no statistically significant difference was found in PI3K protein, PI3K mRNA, Akt protein or Akt mRNA expression level (P＞0.05). The high, medium and low dose groups had significantly higher SOD activity and significantly lower MDA content than the control group(P＜0.05). ConclusionThe ethanol extract of Cyathula officinalis Kuan can decrease pulmonary hypertension induced by monocrotaline, inhibit oxidative stress response and reduce pulmonary vascular remodeling. Its mechanism may be related to down-regulation of PI3K/Akt signaling pathway in lung tissue.