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Deprecated: Implicit conversion from float 265.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Int+J+Mol+Med 2018 ; 42 (2): 926-34 Nephropedia Template TP
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Knockdown of TNF-? alleviates acute lung injury in rats with intestinal ischemia and reperfusion injury by upregulating IL-10 expression #MMPMID29767265
Yang Z; Zhang XR; Zhao Q; Wang SL; Xiong LL; Zhang P; Yuan B; Zhang ZB; Fan SY; Wang TH; Zhang YH
Int J Mol Med 2018[Aug]; 42 (2): 926-34 PMID29767265show ga
Intestinal ischemia and reperfusion (II/R) injury often triggers severe injury in remote organs, with the lungs being considered the main target. Excessive elevation of proinflammatory cytokines is a major contributor in the occurrence and development of II/R-induced acute lung injury (ALI). Therefore, the present study aimed to investigate whether blocking tumor necrosis factor-? (TNF-?) expression could protect the lungs from injury following II/R, and to explore the possible underlying mechanism involving interleukin-10 (IL-10). Briefly, II/R was induced in rats by 40 min occlusion of the superior mesenteric artery and celiac artery, followed by 8, 16 or 24 h of reperfusion. Subsequently, lentiviral vectors containing TNF-? short hairpin (sh)RNA were injected into the right lung tissues, in order to induce TNF-? knockdown. The severity of ALI was determined according to lung injury scores and lung edema (lung wet/dry weight ratio). The expression levels of TNF-? were analyzed by quantitative polymerase chain reaction (qPCR), western blotting and immunofluorescence (IF) staining. IL-10 expression, in response to TNF-? knockdown, was detected in lung tissues by qPCR and IF. The results detected marked inflammatory responses, and increased levels of lung wet/dry weight ratio and TNF-? expression, in the lungs of II/R rats. Conversely, treatment with TNF-? shRNA significantly alleviated the severity of ALI and upregulated the expression levels of IL-10 in lung tissues. These findings suggested that TNF-? RNA interference may exert a protective effect on II/R-induced ALI via the upregulation of IL-10. Therefore, TNF-? knockdown may be considered a potential strategy for the prevention or treatment of ALI induced by II/R in future clinical trials.
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Int+J+Mol+Med 2018 ; 42 (2): 926-34
