2. Academic Validation
  3. Involvement of the p38 MAPK-pHsp27 pathway in vascular hyporeactivity induced by obstructive jaundice in rats

Involvement of the p38 MAPK-pHsp27 pathway in vascular hyporeactivity induced by obstructive jaundice in rats

  • Biomed Pharmacother. 2020 Jan;121:109304. doi: 10.1016/j.biopha.2019.109304.
Hui-Ting Di 1,  Xiao-Zhi Wu 2,  Hong-Qian Wang 3,  Mo Chen 3,  Er-Liang Kong 3,  Wei-Feng Yu 4,  Fei-Xiang Wu 5
Affiliations

Affiliations

  • 1 Department of Anesthesiology & Intensive Care, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, 200438, China; Department of Anesthesiology, Women's Hospital, School of Medicine, Zhejiang University, China.
  • 2 Department of Anesthesiology & Intensive Care, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, 200438, China; Department of Anesthesiology, Dongfang Hospital, Fujian, 354200, China.
  • 3 Department of Anesthesiology & Intensive Care, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, 200438, China.
  • 4 Department of Anesthesiology & Intensive Care, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, 200438, China. Electronic address: [email protected].
  • 5 Department of Anesthesiology & Intensive Care, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, 200438, China. Electronic address: [email protected].
PMID: 31810142 DOI: 10.1016/j.biopha.2019.109304
Abstract

Patients with obstructive jaundice are prone to develop cardiovascular complications during surgery. However, the underlying mechanisms remain largely unknown. The present study was aimed to investigate the role of p38 MAPK-pHsp27 pathway in vascular hyporesponsiveness induced by obstructive jaundice. Firstly, an experimental rat obstructive jaundice model was established by bile duct ligation (BDL). We found that the thoracic aorta rings isolated from BDL rats showed decreased response to norepinephrine and acetylcholine, while continuous intraperitoneal injection with SB203580, a selective p38 MAPK Inhibitor, could significantly prevented BDL-induced hyporeactivity. Also, the immunohistochemistry and Western blot assays revealed that the up-regulation of pHsp27 and F-actin in thoracic aorta rings from BDL rats and bilirubin-treated vascular smooth muscle cells (VSMCs) were also inhibited by SB203580. Moreover, we identified that bilirubin could induced decreased cell proliferation of VSMCs by using CCK8 assay and which was also prevented by SB203580. All these data demonstrated that p38 MAPK-pHsp27 mediates vascular hyporesponsiveness in rats with obstructive jaundice by modulating the expression level of pHsp27 and F-actin, and that inhibition of p38 MAPK signaling could remodel the vascular activity.

Keywords

Actin; Heat shock protein 27; Obstructive jaundice; P38 MAPK; Vascular hyporesponsiveness; Vascular smooth muscle cell.

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