[Effect of sesamin on pulmonary vascular remodeling in rats with monocrotaline-induced pulmonary hypertension].
OBJECTIVE
To observe the effect of sesamin (Ses) on pulmonary vascular remodeling in rats with monocrotaline ( MCT)-induced pulmonary hypertension (PH).


METHODS
Totally 48 male Sprague-Dawley (SD) rats were fed adaptively for one week and then divided into the normal control group, the MCT group, the MCT +Ses (50 mg x kg(-1)) group and the MCT + Ses (100 mg x kg(-1)) group, with 12 rats in each group. The PH rat model was induced through the subcutaneous injection with MCT(60 mg x kg(-1)). After the administration for four weeks, efforts were made to measure the right ventricular systolic pressure( RVSP) and mean pulmonary artery pressure (mPAP) through right jugular vein catheterization, and isolate right ventricle( RV) and left ventricle( LV) +septum (S) and measure their length to calculate RV/ ( LV + S) and ratio of RV to tibial length. Pathologic changes in arterioles were observed by HE staining. Masson's trichrome stain was used to demonstrate changes in collagen deposition of arterioles. The alpha-smooth muscle actin (alpha-SMA) expression in pulmonary arteries was measured by immunohistochemisty. The total antioxidative capacity (T-AOC) and malondialdehyde (MDA) content in pulmonary arteries were determined by the colorimetric method. The protein expressions of collagen I, NOX2 and NOX4 were analyzed by Real-time PCR and Western blot.


RESULTS
After the administration for 4 weeks, Ses could attenuate RVSP and mPAP induced by MCT, RV/ (LV + S) and ratio of RV to Tibial length, alpha-SMA and collagen I expressions and remodeling of pulmonary vessels and right ventricle. Meanwhile, Ses could obviously inhibit the expressions of NOX2, NOX4 and MDA content and increase T-AOC.


CONCLUSIONS
Sesamin could ameliorate pulmonary vascular remodeling induced by monocrotaline in PH rats. Its mechanism may be related to expressions of NOX2 and NOX4 expression and reduction in oxidative stress injury.
Xian-wei
XW
Li
Yun-xing
YX
Gao
Shu
S
Li
Jie-ren
JR
Yang
D000818:Animals; D004149:Dioxoles / Q000008:administration & dosage*; D004195:Disease Models, Animal; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage*; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics / Q000503:physiopathology; D017705:Lignans / Q000008:administration & dosage*; D008168:Lung / Q000098:blood supply / Q000201:enzymology / Q000378:metabolism; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D016686:Monocrotaline / Q000009:adverse effects; D000074662:NADPH Oxidase 2; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases / Q000235:genetics / Q000378:metabolism; D011651:Pulmonary Artery / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D066253:Vascular Remodeling / Q000187:drug effects*
D004149:Dioxoles; D004365:Drugs, Chinese Herbal; D017705:Lignans; D008562:Membrane Glycoproteins; D016686:Monocrotaline; C500593:Cybb protein, rat; D000074662:NADPH Oxidase 2; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases; C498911:Nox4 protein, rat; C054125:sesamin