野百合碱诱导大鼠肺动脉高压时对肺血管壁Jagged2/Notch3信号分子表达的影响

Expression of Jagged2/Notch3 signaling molecules in pulmonary hypertensive rats induced by monocrotaline

目的:观察野百合碱诱导大鼠肺动脉高压时肺血管壁Jagged2/Notch3信号分子表达的变化,探讨Jagged2/Notch3信号在肺动脉高压发生中的作用和意义。方法:45只SD大鼠随机分为正常对照组(C组)、溶剂对照组(S组)和野百合碱模型组(M组),每组15只,通过一次性腹腔注射野百合碱50 mg/kg建立肺动脉高压模型,溶剂对照组注射相同剂量的溶媒。4周时通过HE染色观察肺血管重构,通过右心导管测定平均肺动脉压(m PAP)和右心室收缩压(RVSP)。采用免疫组化和实时荧光定量PCR等方法检测肺血管壁Jagged2/Notch3/Hes5蛋白和mRNA表达的变化。结果:与正常对照和溶剂对照组相比,4周时野百合碱模型组的血管壁显著增厚,中膜厚度百分比增加(P<0.01);此外野百合碱模型组的m PAP和RVSP显著高于正常对照和溶剂对照组(P<0.01);免疫组化和实时荧光定量PCR结果提示Jagged2主要表达于肺小动脉内膜,Notch3、Hes5主要表达于肺小动脉中层平滑肌,与溶剂对照组以及正常对照组相比,野百合碱模型组肺小动脉的Jagged2、Notch3和Hes5表达显著增高。结论:Jagged2/Notch3信号分子的激活可能在野百合碱诱导肺动脉高压发生中起重要作用。

AIM：To study the expression of Jagged 2/Notch3 signaling molecules in pulmonary vascular wall of pulmonary hypertensive rats induced by monocrotaline .METHODS： SD rats were randomly divided into normal control group （C group,n=15）, solvent control group （S group,n=15） and monocrotaline model groups （M group,n=15）.The model of pulmonary hypertension was established by a single subcutaneous injection of monocrotaline （50 mg/kg）.The rats in S group were given a single subcutaneous injection of the same dose of solvent .After 4 weeks, the pulmonary vascular remodeling was assessed by HE staining , and the mean pulmonary artery pressure （ mPAP） and right ventricular systolic pressure （RVSP） were determined by right heart catheterization .The expression of Jagged2/Notch3 /Hes5 molecules in the pulmonary vascular wall was detected by immunohistochemical method and real -time PCR.RESULTS：Compared with S group and C group , the percentage of medial wall thickness of smaller arteries in model group increased significantly （P〈0.01）.The levels of mPAP and RVSP in M group were significantly higher than those in S group and C groups （P〈0.01）.The results of real-time PCR showed that the expression of Jagged 2, Notch3 and Hes5 was significantly increased in M group compared with S group and C group .The data from immunohistochemical detection indicated that Jagged 2 mainly expressed in the intima of small lung artery , Notch3 and Hes5 mainly expressed in the medial smooth muscle cells .Com-pared with S group and C group , the expression of Jagged 2 and Notch3 was significantly increased in the lung small arteries of M group.CONCLUSION：The activation of Jagged2/Notch3 signaling pathway might play an important role in the for-mation of pulmonary hypertension .