Treatments Of Cyclosporin A, Ginsenoside Rb1and Notoginsenoside R1in Two Widely Experimental Models Of Pulmonary Hypertension Rats

The typical vascular pathological states in the development of pulmonaryhypertension （PH） are due to Ca²⁺homeostasis imbalance in pulmonary vascularsmooth muscle cells （PASMCs）.Previous studies of PH pathogenesis show thatcanonical transient receptor potential （TRPC） is the major constituent ofstore-operated Ca²⁺channel（SOCC） and TRPC genes are upregulated andstoreoperated Ca²⁺entry （SOCE） is augmented in PASMCs of monocrotaline（MCT）and chronic hypoxic rats. In the present study, PH rats were simulated by means ofMCT injection and chronic hypoxia （CH） to reflect different PH characteristics, andthen, CosA was intraperitoneally injected at a dose of35mg/kg on alternate days toestablish CosA preventing MCT and CH-induced PH rat model. In addition，traditional herb-medicine Ginsenoside（Rb1）and Notoginsenoside（R1）were appliedto de-endothelial PAs of MCT and CH-treated rats. Identified the effects of the twopre-treat methods, and then find new therapeutic targets for pharmacotherapy of PH.1. The therapeutical effect of cyclosporin A in the development of MCT andCH-induced PH.Objective: To investigate the intervention effects of cyclosporin in the developmentof MCT and CH-induced PH, further examine the mechanism of action of CosA, andfind new therapeutic targets for pharmacotherapy of PH.Methods: a dose of50mg/kg （BW） MCT was given to SD rats by singleintraperitoneal injection as MCT-group and another model was exposured with CH（10%oxygen） within21days,during the time, CosA was intraperitoneally injected at a dose of35mg/kg on alternate days to establish CosA interfered MCT andCH-induced PH rat models. The observation items:①mRVSP, MRVP and RVMI;②CPA-induced vasoconstriction;③ET-1-induced dose-dependent contraction in PAs;④the inhibition of ET-1-induced vasoconstriction by Gd³⁺.Results: Compared with MCT and CH-treated rats, CosA intervention3w：①mRVSP, MRVP and RVMI were dramatically decreased in CosA;②BluntedCPA-induced vasoconstriction;③Attenuated ET-1response in MCT and CH PAs;④Enhanced the inhibition of ET-1-induced vasoconstriction by Gd³⁺.Conclusion: CosA intervention3w prevented MCT and CH–induced PH, pulmonaryartery proliferation and cardiac hypertrophy， and blunted SOCE-inducedvasoconstriction and ET-1response.2. The vasodilation effect of Ginsenoside Rb1and Notoginsenoside R1upon theisolated PAs in MCT and CH-induced PH ratsObjective: On the basis of PH, attempt to observe the effects of Ginsenoside Rb1andNotoginsenoside R1in the regulating of pulmonary artery tone to explore newpharmacotherapy for PH.Methods: A dose of50mg/kg （BW） MCT was given to SD rats by singleintraperitoneal injection as MCT-group and another model was exposured with CH(10%oxygen, feeding normally for21days. We observe:①mRVSP, MRVP, RVMI;②the dose-dependently inhibition caused by Ginsenoside Rb1and NotoginsenosideR1;③the relaxation of ET-1and CPA pre-contraction PAs induced by GinsenosideRb1and Notoginsenoside R1, respectively;④Ginsenoside Rb1and NotoginsenosideR1inhibition effect after relaxation of inhibition of ET-1-induced vasoconstriction byGd³⁺.Results:①Ginsenoside Rb1and Notoginsenoside R1dose-dependently inhibited theET-1-induced contraction of CON rats, respectively;②Ginsenoside Rb1andNotoginsenoside R1partly inhibition the ET-1and CPA-induced vasoconstriction inPH rats, respectively;③Ginsenoside Rb1and Notoginsenoside R1exhibition nosignificant inhibition effect after relaxation of inhibition of ET-1-induced vasoconstriction by Gd3.Conclusion: Ginsenoside Rb1and Notoginsenoside R1maypartly inhibition the signaling pathway of Ca²⁺in pulmonary artery smooth musclecells（PASMCs）, and blunt the TRPC/SOCE-induced vasoconstriction.