| Pulmonary hypertension(PH) is a kind of cardiovascular disease, which is mainly manifested by the increase of pulmonary pressure, the remodeling of pulmonary artery and the increase of Ca2+ in cytoplasm. The process is a complicated pathological process.Recent studies have shown that canonical transient receptor potential(TRPC) proteins, stromal interaction molecule(STIM) and Orai are important molecules in activation of sotre-operated calcium entry(SOCE), nuclear factor of activated T cells(NAFTc) related to cell proliferation, and TRPC/SOCE is augmented in chronic hypoxia(CH)-induced PH(CHPH) and monocrotaline-induced PH rats. Ginsenoside Rb1 as a steroid compounds, can reduce the concentration of intracellular calcium ion and plays a major role in anti-oxidation and resistance to myocardial hypertrophy. Previous studies have indicated that Rb1 can block the calcium channel of cardiac muscle and resist the injury caused by myocardial ischemia, and it can inhibit the proliferation of smooth muscle cells through its antioxidant and Ca N pathway. However, there is no report that whether administration of Rb1 can fight pulmonary hypertension in vivo.Objective: This study was mainly to observe the changes of pulmonary artery pressure and the function index of pulmonary artery smooth muscle cells during the development of pulmonary hypertension, to explore whether Rb1 can resist the occurrence and development of pulmonary hypertension.Methods: In this study, we established the PH rat model induced by Monocrotaline(MCT) and, and observed the effect of Rb1 on pulmonary artery pressure and pulmonary artery smooth muscle cell function by intraperitoneal injection of Rb1.Results:(1)Compared with normal control group(CON), RVMI and m RVSP were significantly increased in MCT rats, and the smooth muscle layer of the pulmonary artery was obviously thickened and the lumen was decreased. The proliferation and migration of PAMSCs were significantly increased, and the apoptosis was decreased in the MCT group.(2)Rats intraperitoneally infused with Rb1. Rb1 intervention can significantly decrease the RVSP and RVMI of the MCT rats, which from 76.95±10.10 mm Hg to 49.3±9.10 mm Hg and 62.75±7.66% to 34.99±4.74% respectively.(3)Compared with MCT rats, the increase of PASMCs[Ca2+]i in rats with Rb1 was significantly decreased, from 415.64±22.23 n M to 253.04±32.65 n M, resting [Ca2+]i decreased significantly, from 131.2 to 12.9 n M, to 69.1 + 28.9 n M.(4)Compared with MCT group, Rb1 intervention group PCNA protein expression is reduced, the OD value is determined by MTT method; Compared with MCT group, Rb1 intervention group migration cells was reduced.(5)Compared with MCT group, STIM2,TRPC1/4, Ca NB?,NFAT3/4 m RNA and protein expression is reduced in Rb1 intervention group,, Orai1 did not differ between the m RNA and protein expression, Orai2 m RNA expression is reduced, but protein expression has not changed.Conclusion: MCT rats by intraperitoneal injection of Rb1 can improve the occurrence and development of pulmonary hypertension. Its mechanism may be caused by Rb1 intervention reduce the up-regulation of SOCE function in MCT rats, which leads to the decrease of resting [Ca2+]i so as to reduce the PAs vascular contraction and remodeling. |
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