title: Activation of PPARγ by baicalin attenuates pulmonary hypertension in an infant rat model by suppressing HMGB1/RAGE signaling.
abstract: Pulmonary hypertension (PH) is a vascular disease, and proinflammatory factors are strongly implicated in its pathogenesis, causing right ventricular (RV) hypertrophy and heart failure. Baicalin exhibits potent anti-inflammation activity. This study aimed to investigate the curative effects of baicalin in an infant rodent model of PH and to further explore the underlying mechanisms. A PH model in infant rats was induced by hypoxia and the resulting rats were administered baicalin in incremental dosages. Invasive hemodynamic methods were used to measure mean pulmonary arterial pressure (mPAP) and RV end-diastolic pressure (RVEDP). RV hypertrophy was assessed by mass pathology and histology. ELISAs were used to determine concentrations of high-mobility group box 1 (HMGB1), secretory receptor for advanced glycation end products (sRAGE), interleukin 6 (IL6) and transforming growth factor β (TGFβ1) in bronchoalveolar lavage fluid (BALF). Electrophoretic mobility shift and phosphorylation in nuclear extracts were used to evaluate the activation of peroxisome proliferator-activated receptor γ (PPARγ). Western blotting was used to detect the expression levels of heme oxygenase 1 (HO1), HMGB1, RAGE, IL6 and TGFβ1 in lung tissue. Baicalin administration significantly attenuated mPAP, RVEDP and RV hypertrophy in infant rats with PH. HMGB1, sRAGE, IL6 and TGFβ1 levels in BALF were also reduced by baicalin treatment. Baicalin activated PPARγ, which promoted expression of HO1. Furthermore, expression levels of HMGB1, RAGE, IL6 and TGFβ1 in lung tissue were dramatically decreased by baicalin in a dosage-dependent manner. Baicalin showed curative effects in infant rats with PH. Activation of PPARγ that inhibited HMGB1/RAGE inflammatory signaling was involved.
authors.affiliation: Department of PICU The Children's Hospital Zhejiang University School of Medicine Hangzhou China.
authors.forename: Zhenjie
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Department of PICU The Children's Hospital Zhejiang University School of Medicine Hangzhou China.
authors.forename: Qiuxia
authors.initials: Q
authors.lastname: Wang
keywords: PPARγ; baicalin; infants; inflammation; pulmonary hypertension