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[高肺血流量对肺血管结构及胱硫醚-γ-裂解酶基因表达的影响]

[Effects of high pulmonary blood flow on pulmonary vascular structure and the gene expression of cystathionine-gamma-lyase].

作者信息

Shi Lin, Du Junbao, Pu Dingfang, Qi Jianguang, Wei Bing, Tang Chaoshu, Tang Xiuying

机构信息

Department of Pediatrics, Peking University First Hospital, Beijing 100034, China.

出版信息

Beijing Da Xue Xue Bao Yi Xue Ban. 2003 Dec 18;35(6):566-70.

Abstract

OBJECTIVE

To examine the alteration of pathologic structure and endogenous hydrogen sulfide pathway in rats with pulmonary hypertension induced by high pulmonary blood flow.

METHODS

Sixteen SD rats were randomly divided into shunting group and control group. An 11-week aortocaval shunting was produced in rats of shunting group, and pulmonary artery mean pressure (mPAP) was evaluated using right cardiac catheterization. The ratios of right ventricular mass to body weight (RV/BW) and right ventricular mass to left ventricular plus septal mass [RV/(LV+S)] were also detected. Pulmonary vascular micro- and ultra- structures were examined. Meanwhile the concentration of plasma hydrogen sulfide (H(2)S) was measured by spectrophotography. The gene expression of cystathionine-gamma-lyase (CSE)was detected by in situ hybridization, and the activity of CSE in lung tissues was measured by H(2)S production according to chemical analysis. RESULTS After 11 weeks of aortocaval shunting, pulmonary artery mean pressure was significantly increased. Muscularization of small pulmonary vessels and relative medial thickness of pulmonary arteries were obviously increased in shunting rats compared with controls. Ultrastructure of intrapulmonary arteries changed obviously in shunting rats. Meanwhile, plasma H(2)S concentration was decreased and the activity of CSE (according to H(2)S production) in lung tissues decreased in shunting rats. CSEmRNA expression by pulmonary arteries was significantly suppressed.

CONCLUSION

Pulmonary vascular structural remodeling is the important pathologic basis for pulmonary hypertension induced by high pulmonary blood flow. The down-regulation of endogenous H(2)S pathway might play an important role in the development of high pulmonary blood flow induced pulmonary hypertension.

摘要

目的

探讨高肺血流量致肺动脉高压大鼠病理结构及内源性硫化氢通路的变化。

方法

将16只SD大鼠随机分为分流组和对照组。对分流组大鼠行11周的主动脉腔静脉分流术,采用右心导管法测定肺动脉平均压(mPAP)。检测右心室质量与体重比值(RV/BW)及右心室质量与左心室加室间隔质量比值[RV/(LV+S)]。观察肺血管的微观和超微结构。同时,采用分光光度法测定血浆硫化氢(H₂S)浓度。采用原位杂交法检测胱硫醚-γ-裂解酶(CSE)的基因表达,根据化学分析法通过检测H₂S生成量测定肺组织中CSE的活性。结果 主动脉腔静脉分流11周后,肺动脉平均压显著升高。与对照组相比,分流组大鼠肺小血管肌化及肺动脉相对中膜厚度明显增加。分流组大鼠肺内动脉超微结构明显改变。同时,分流组大鼠血浆H₂S浓度降低,肺组织中CSE活性(根据H₂S生成量)降低。肺动脉CSEmRNA表达明显受抑。

结论

肺血管结构重塑是高肺血流量致肺动脉高压的重要病理基础。内源性H₂S通路下调可能在高肺血流量致肺动脉高压的发生发展中起重要作用。

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