Role of myosin heavy chain 9 in gut-vascular barrier damage in septic mice
10.3760/cma.j.cn131073-20240717-00415
- VernacularTitle:肌球蛋白重链9在脓毒症小鼠肠道-血管屏障损伤中的作用
- Author:
Ruili DING
1
;
Chuanbing ZHAO
;
Jie LUO
;
Rong CHEN
;
Qingtao MENG
Author Information
1. 武汉大学人民医院麻醉科,武汉 430060
- Publication Type:Journal Article
- Keywords:
Myosin heavy chain;
Sepsis;
Gut-vascular barrier
- From:
Chinese Journal of Anesthesiology
2025;45(4):463-468
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To evaluate the role of myosin heavy chain 9(MYH9) in gut-vascular barrier damage in septic mice.Methods:Eighty SPF C57BL/6J male mice, aged 6-8 weeks, weighing 20-25 g, were divided into 4 groups( n=20 each) by the random number table method: sham operation group(Sham group), sham operation + MYH9 inhibitor blebbistatin group(Sham+ Ble group), cecal ligation and perforation(CLP) group, and CLP+ blebbistatin group(CLP+ Ble group). A mouse sepsis model was established using CLP in anesthetized animals. Blebbistatin solution 5 mg/kg was intraperitoneally injected at 1 h before CLP in Sham+ Ble and CLP+ Ble groups, while the equal volume of phosphate buffer was given instead in Sham and CLP groups. Fourteen mice were randomly selected from each group to observe the survival at 24 h after CLP. Blood samples were taken by apical puncture at 24 h after surgery in the remaining 6 mice in each group for determination of the plasma concentrations of tumor necrosis factor-α(TNF-α), interleukin-1β(IL-1β) and interleukin-6(IL-6)(using enzyme-linked immunosorbent assay), expression of plasma membrane vesicle-associated protein(PLVAP) in intestinal microvascular endothelial cells(using immunofluorescence), and expression of MYH9, PLVAP, vascular endothelial calreticulin(VE-cadherin) and β-catenin protein and mRNA(by Western bot or fluorescent quantitative real-time polymerase chain reaction) and for examination of the pathological changes of intestinal tissues. Intestinal damage was assessed and scored according to Chiu. Results:Compared with Sham group, the expression of MYH9 protein and mRNA was significantly down-regulated in Sham+ Ble group, and the survival rate was significantly decreased at 24 h after surgery, Chiu′s scores in intestinal tissues were increased, the plasma concentrations of TNF-α, IL-1β and IL-6 were increased, the expression of PLVAP in intestinal microvascular endothelial cells was up-regulated, the expression of MYH9 and PLVAP protein and mRNA in intestinal tissues was up-regulated, and the expression of VE-cadherin and β-catenin protein and mRNA was down-regulated in CLP group( P<0.05). Compared with CLP group, the survival rate was significantly increased at 24 h after surgery, Chiu′s scores in intestinal tissues were decreased, the plasma concentrations of TNF-α, IL-1β and IL-6 were decreased, the expression of PLVAP in intestinal microvascular endothelial cells was down-regulated, the expression of MYH9 and PLVAP protein and mRNA in intestinal tissues was down-regulated, and the expression of VE-cadherin and β-catenin protein and mRNA was up-regulated in CLP+ Ble group( P<0.05). Conclusions:MYH9 is involved in gut-vascular barrier damage in septic mice.