Research Of The Effect Of Curcumin On Pulmonary Hypertension And It's Mechanism

Pulmonary hypertension is a progressive clinical syndrome featuring increased pulmonary vascular resistance which is caused by pulmonary vascular bed structure and/or functional changes. Ultimately resulting in right ventricular expansion, causing heart failure and even death. Multifactorial pathobiological factors such as vasoconstriction, pulmonary vascular remodeling, thrombus formation are involved in the disease process of pulmonary arterial hypertension (PAH). Pulmonary microvascular wall constriction and remodeling contribute to increased pulmonary vascular resistance in PAH[1-3]. Proliferation of pulmonary microvascular smooth muscle cells (PMSMCs) and extension of these cells into nonmuscular vessels are typical features of pulmonary vascular remodeling[1,4]. Pharmacological therapies targeting the PMSMCs proliferation might be valuable strategies for the treatment of PAH.Curcumin (diferuloylmethane), a polyphenol responsible for the yellow color of the curry spice turmeric and a known polyphenol with anti-inflammatory, anti-oxidant, anti-carcinogenic, anti-thrombotic, and cardiovascular protective effects, has been showed to be a specific inhibitor of p300 and could block vascular smooth muscle cells proliferation and attenuate cardiac hypertrophy[5,6]. It has been reported that curcumin may also improve several diseases, including several types of cancer[7], rheumatoid arthritis[8], psoriasis[9],Alzheimer's disease[10] and epilepsy[10].The protective effects of curcumin on the cardiovascular system have been studtied previously.However, till now,the effects of curcumin on pulmonary arterial hypertension and related molecular mechanism are well unknown.In this study, we testified the hypothesis that the protective effects of curcumin on pulmonary arterial hypertension and related molecular mechanism therefore, might be a potential therapeutics for PAH. The paper is composed of two sections.Partâ… . Effect of curcumin on rat pulmonary arterial hypertensionObjective:To explore the effect of curcumin on rat pulmonary arterial hypertension.Methods:Our hypotheses was tested in a modle of pulmonary arterial hypertension induced by monoerotaline in rats.(pulmonary arterial hypertension are developed Significantly after 4 weeks). The rats were divided into control group, pulmonary arterial hypertension group plus curcumin group. Curcumin group was subdivided into three dosage group.they are 200mg/kg.d,100mg/kg.d and 50 mg/kg.d. After 4 weeks, we detected rat pulmonary artery pressure,the ratio of right ventricle to body weight. Lung tissue is fixed by formalin, Paraffin-embedded, H.E staining of rat lung blood vessel.Results:Curcumin can decrease rat pulmonary arterial pressure and the ratio of right ventricle to body weight. The result of H.E staining shows curcumin can attenuate the wall thickening and stenosis of rat lung blood vessel.Conclusions:Curcumin may protect pulmonary hypertensive rats induced by monocrotaline via inhibiting lung vascular remodeling.Partâ…¡. The effect of curcumin on the proliferation and cell cycle of pulmonary microvascular smooth muscle cells in ratsObjective:To culture pulmonary microvascular smooth muscle cells (PMSMCs) and explore the effect of curcumin on the proliferation and cell cycle of PMSMCs and the possible molecular mechanism.Methods:Pulmonary microvascular smooth muscle cells were isolated, identified, cultured. The proliferation of the cells was measured by MTT colorimetric Assay. Cell cycle was analyzed by Flow Cytometry. The expression of mRNA and proteins were detected by RT-PCR and Western blot.Results:Curcumin inhibited the PMSMCs proliferation in a concentration dependent manner. Curcumin arrested the progression of cell cycle at G0/G1 phase. Moreover, curcumin upregulated the expression of p53 and p21 and downregulted the protein level of p300 and the acetylation of H3 and p53 mediated by p300. Conclusions:The results indicate that curcumin can inhibit PMSMCs proliferation and arrest the progression of cell cycle at G0/G1 phase via downregulating p300 activity and upregulating p53 related signaling.