The effect and mechanism of glyburide on monocrotaline-induced pulmonary hypertension in rats

doi:10.3969/j.issn.1006-7795.2015.05.012

Abstract

Abstract: Objective To investigate whether glyburide could prevent monocrotaline (MCT)-induced pulmonary hypertension (PH) via inhibiting nucleotide-binding domain and leucine-rich repeat PYD-containing protein 3 (NLRP3) inflammasome activation in rats. Methods Male Sprague-Dawley (SD) rats were divided into 3 groups: control group, MCT group and MCT+glyburide group. Hemodynamic changes, right ventricular hypertrophy, and lung morphological features were assessed. The levels of NLRP3 and interleukin-1β(IL-1β) were assessed by Western blotting and ELISA. Results Compared with control group, four weeks after MCT injection, the right ventricular systolic pressure (RVSP), the index of right ventricular hypertrophy (RVHI) and the percentage of medial thickness (MT%) of pulmonary artery significantly increased by 1.66 (P<0.001), 2.15(P<0.001) and 1.20 folds (P<0.001), respectively. Compared with MCT group, they reduced by (33.60±5.14)% (P<0.05), (18.26±9.23)% (P<0.05) and (21.86±8.64)% (P<0.001) in MCT+glyburide group. Compared with control group, the expression of NLRP3 in lung of MCT group increased by 1.57 folds (P<0.05), while it decreased by (55.96±19.33)% (P<0.01) after using glyburide in 4 weeks. The serum level of IL-1β was higher in MCT group than that in control group[ (1 915.82±316.47)pg/mL vs (118.29±27.60)pg/mL, P<0.001], while it was lower in MCT+glyburide group than that in MCT group [(396.64±237.19)pg/mL vs (1 915.82±316.47)pg/mL, P<0.001]. Conclusion These results suggested that glyburide could ameliorate MCT-induced pulmonary hypertension that was mediated by the NLRP3/IL-1β pathway.

Key words: glyburide, NLRP3, monocrotaline, pulmonary hypertension

CLC Number:

R363

Liu Ting, Liu Yafei, Wang Wang, Chai Sanbao, Liu Jie, Wang Jun. The effect and mechanism of glyburide on monocrotaline-induced pulmonary hypertension in rats[J]. Journal of Capital Medical University, 2015, 36(5): 723-728.

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URL: https://journal03.magtech.org.cn/Jweb_sdykdxxb/EN/10.3969/j.issn.1006-7795.2015.05.012

https://journal03.magtech.org.cn/Jweb_sdykdxxb/EN/Y2015/V36/I5/723

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