The comparative study of calcium-dependent and calcium-independent of dephosphorylation of myosin light chain and its effect on pulmonary artery pressure and right ventricular remodeling in rats / 中华实用儿科临床杂志

ABSTRACT

Objective To investigate the effects of calcium - dependent and calcium - independent in myosin light chain(MLC)dephosphorylation on pulmonary hemodynamics and right ventricular remodeling,and to observe whether there is a superimposition effect while intervention is conducted in two ways at the same time. Methods Ac-cording to random number table,50 rats were divided into 5 groupssham operation group,model group,3 mg/(kg·d) ML - 7[MLC kinase(MLCK)inhibitor]treating group(M group),20 mg/(kg·d)Fasudil(Rho kinase inhibitor) treating group(F group)and 3 mg/(kg·d)ML - 7 plus 20 mg/(kg·d)Fasudil treating group(M + F group). The shunt between the abdominal aorta and inferior vena cava was used to establish rat models of pulmonary hypertension in-duced by high pulmonary flow in group of C and the experimental groups. The sham operation group was given a sham operation. MLCK and Rho kinase inhibitor were administrated intraperitoneally to rats with the shunt. After 8 weeks of shunting,mean right ventricular pressure(MRVP),mean pulmonary arterial pressure(MPAP),right ventricular hyper-trophy index(RVHI)and width of inferior venacava were evaluated by the right cardiac catheterization procedure. Results Compared with the sham operation group,MRVP,MPAP,and RVHI were obviously elevated in the model group [(2. 65 ±0. 57)kPa vs(4. 19 ±0. 67)kPa;(2. 42 ± 0. 48)kPa vs(4. 04 ± 0. 61)kPa,F = 295. 368,263. 912,all P ﹤0. 01;(0. 21 ±0. 01)g/ g vs(0. 41 ±0. 03)g/ g,F =247. 024,P ﹤0. 01]. Compared with model group,the MRVP,MPAP and RVHI in M group and F group were decreased significantly[(3. 51 ± 0. 47)kPa vs(4. 19 ± 0. 67)kPa;(3. 68 ± 0. 55)kPa vs(4. 19 ±0. 67)kPa,all P ﹤0. 01;M group(0. 29 ±0. 02)g/ g,model group(0. 41 ± 0. 03)g/ g,F group (0. 30 ±0. 03)g/ g,F =247. 024,P ﹤0. 05]. But the MRVP,MPAP and RVHI in M group and F group were higher than those of rats in the sham operation group. The MRVP,MPAP and RVHI of M + F group were elevated much obviously compared with those of the M or F group(P ﹤0. 05). Conclusions The calcium - dependent and calcium - independent in MLC dephosphorylation can respectively restrain the development of pulmonary hypertension and right ventricular re-modeling,and the obvious additive effect can be observed when the 2 drugs are used jointly.