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Rosuvastatin Alleviates Intestinal Injury by Down-Regulating the CD40 Pathway in the Intestines of Rats Following Traumatic Brain Injury.

ABSTRACT: Statins have been reported to suppress CD40 expression and nuclear factor (NF)-?B activation, which are both up-regulated in the intestines following traumatic brain injury (TBI)-induced intestinal injury. In this study, we aimed to investigate the effects of the statin rosuvastatin on post-TBI jejunal injury in rats, focusing on potential mechanisms involving the CD40/NF-?B signaling pathway. The jejunal CD40 expression was determined by western blotting. The DNA-binding activity of NF-?B was assessed by electrophoretic mobility shift assays (EMSAs). The tumor necrosis factor (TNF)-? and interleukin (IL)-1? levels were assessed by enzyme-linked immunosorbent assays (ELISAs). The severity of the jejunal mucosal injury was assessed by hematoxylin and eosin (HE) staining and histopathological evaluation. We found that the post-TBI upregulation of both CD40 expression and NF-?B activity in the jejunal tissues were significantly inhibited by rosuvastatin, while the post-TBI expression of TNF-? and IL-1? was significantly suppressed by rosuvastatin. In addition, rosuvastatin significantly ameliorated TBI-induced effects on the villus height, crypt depth, and villous surface area. Rosuvastatin suppressed TBI-induced intestinal injury in rats, which may be associated with the blockade of the CD40/NF-?B pathway.

SUBMITTER: Hu Y

PROVIDER: S-EPMC7431906 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Rosuvastatin Alleviates Intestinal Injury by Down-Regulating the CD40 Pathway in the Intestines of Rats Following Traumatic Brain Injury.

Hu Yangchun Y Wang Xiaojian X Ye Lei L Li Chao C Chen Weiwei W Cheng Hongwei H

Frontiers in neurology 20200811

Statins have been reported to suppress CD40 expression and nuclear factor (NF)-κB activation, which are both up-regulated in the intestines following traumatic brain injury (TBI)-induced intestinal injury. In this study, we aimed to investigate the effects of the statin rosuvastatin on post-TBI jejunal injury in rats, focusing on potential mechanisms involving the CD40/NF-κB signaling pathway. The jejunal CD40 expression was determined by western blotting. The DNA-binding activity of NF-κB was a ...[more]

PMID: 32849246

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Project description:Background and aimsBy blocking TNF?-related effects, thalidomide not only inhibits hepatic fibrogenesis but improves peripheral vasodilatation and portal hypertension in cirrhotic rats. Nonetheless, the investigation of thalidomide's effects on splanchnic and collateral microcirculation has been limited. Our study explored the roles of intestinal and mesenteric TNF? along with inflammasome-related pathway in relation to cirrhosis and the splanchnic/collateral microcirculation.MethodsUsing in vivo and in vitro approaches, mechanisms of the effects of thalidomide on intestinal and mesenteric inflammatory, vasodilatory and angiogenic cascades-related abnormalities were explored in cirrhotic rats that had received 1-month thalidomide (C-T) treatment.ResultsIn cirrhotic rats, high tumor necrosis factor (TNF)?, vascular endothelial growth factor (VEGF) and nitric oxide (NO)x levels were associated with the NOD-like receptors protein 3 (NLRP3), IL-1? and caspase-1 inflammasome over-expression in splenorenal shunt and mesenteric tissues. The thalidomide-related inhibition of mesenteric and splenorenal shunt inflammasome expression was accompanied by a significantly decreased intestinal mucosal injury and inflammasome immunohistochemical staining expression. Suppression of various angiogenic cascades, namely VEGF-NOS-NO, was paralleled by a decrease in mesenteric angiogenesis as detected by CD31 immunofluorescence staining and by reduced portosystemic shunting (PSS) in C-T rats. The down-regulation of the mesenteric and collateral vasodilatory VEGF-NOS-NO cascades resulted in a correction of vasoconstrictive hypo-responsiveness and in an attenuation of vasodilatory hyper-responsiveness when analyzed by in situ perfusion of the superior mesenteric arterial (SMA) and portosystemic collaterals. There was also a decrease in SMA blood flow and an increase in SMA resistance in the C-T rats. Additionally, acute incubation with thalidomide abolished TNF?-augmented VEGF-mediated migration of and tube formation of human umbilical vein endothelial cells, which was accompanied by corresponding changes in inflammatory and angiogenic substances release.ConclusionsThe suppression of inflammasome over-expression by chronic thalidomide treatment ameliorates inflammatory, angiogenic and vasodilatory cascades-related pathogenic changes in the splanchnic and collateral microcirculation of cirrhotic rats. Thalidomide seems to be a promising agent that might bring about beneficial changes to the disarrangements of peripheral, hepatic, splanchnic and collateral systems in cirrhosis.

Dataset Information

Rosuvastatin Alleviates Intestinal Injury by Down-Regulating the CD40 Pathway in the Intestines of Rats Following Traumatic Brain Injury.

Publications

Rosuvastatin Alleviates Intestinal Injury by Down-Regulating the CD40 Pathway in the Intestines of Rats Following Traumatic Brain Injury.

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