二脒那秦在肺动脉高压模型大鼠中的预防和治疗作用

目的探究二脒那秦(DIZE)对肺动脉高压(PAH)模型大鼠的预防及治疗作用。方法采用左肺叶切除联合野百合碱(MCT)腹壁皮下注射建立PAH大鼠模型,100只成年雄性Wistar大鼠随机分成空白对照组(A组)、DIZE对照组(B组)、PAH模型组(C组)、DIZE处理PAH模型组(D组)和(DIZE+C-16)处理PAH模型组(E组),利用活性荧光共振能量转移(FRET)和酶联免疫吸附试验(ELISA)法测定血管紧张素转化酶2(ACE2)、血清IL-6及IL-8水平,并测定平均肺动脉压(m PAP)、右心室肥厚指数(RVHI),计算中膜厚度与肺动脉外径的比例(WT)、内膜增生评分,并通过弹力纤维染色分析肺血管病变。结果 RVHI、ACE2酶活性、WT及内膜增生评分比较:与A组比较,C组、D组和E组差异有统计学意义(P0.05);D组和E组差异有统计学意义(P0.05)。五个组在各个指标整体分析中差异有统计学意义(P0.05)。结论二脒那秦可以提高ACE2酶活性,并有效降低m PAP、RVHI和WT,同时减轻肺动脉中膜肥厚,并抑制肺小动脉内膜增生。该研究结论为二脒那秦治疗人类PAH提供实验基础。

Preventive and therapeutic effect of diminazene in the rat model of pulmonary arterial hypertension

Objective To explore the preventive and therapeutic effects of diminazene (DIZE) on pulmonary arterial hypertension (PAH) in rats. Methods Left pulmonary lobectomy combined with injection of monocrotaline was used to establish a rat model of pulmonary arterial hypertension. One hundred adult male Wistar rats were randomly divided into blank control group (group A, n=20), DIZE control group (group B, n=20), PAH model group (group C, n=20), PAH model plus DIZE group (group D, n=20) and PAH model plus DIZE and C-16 group (group E, n=20). Angiotensin-converting enzyme 2 (ACE2), IL-6 and IL-8 levels were determined by fluorescence resonance energy transfer (FRET) and enzyme linked immunosorbent assay (ELISA), and the mean pulmonary arterial pressure (mPAP) and right ventricular hypertrophy index (RVHI) were measured. The wall thickness (WT) and intimal hyperplasia score were calculated, and the pulmonary vascular lesions were analyzed using elastic fiber staining. Results RVHI, ACE2 enzyme activity and WT in the group A were significantly different from those of the groups C, D and E (P<0.05). Those of the group D and E were significantly different (P<0.05). The five groups showed significant differences in the overall analysis of each index (P<0.05). Conclusions Diminazene can increase the ACE2 enzyme activity, and decrease the mPAP, RVHI and WT, while reducing the pulmonary arterial medial hypertrophy, and inhibit intimal hyperplasia of pulmonary arterioles. The results of this study provide an experimental basis for the use of diminazene in the treatment of human pulmonary hypertension.