ABSTRACT
Background: Expression of microRNA⁃320 (miR⁃320) is down regulated in acute pancreatitis, and the mechanism of its effect on acute pancreatitis is still unclear. Aims: To investigate the effect of miR⁃320 on intestinal injury in rats with acute pancreatitis and its mechanism. Methods: Rats were randomly divided into sham operation group, model group, miR⁃ 320 agonist group (agomir miR ⁃ 320 group), miR ⁃ 320 agonist control group (agomir NC group), JAK2 inhibitor group (AG490 group), and NF⁃κB pathway inhibitor group (PDTC group). The rat model of acute pancreatitis was established by retrograde injection of 5% sodium taurocholate to the bile duct. The automatic biochemical analyzer was used to detect serum levels of amylase and lipase; ELISA assay was used to detect serum levels of TNF⁃α and IL⁃1β; HE staining was used to observe the pathological changes of rat pancreas and ileum; TUNEL staining was used to observe cell apoptosis in rat ileum; real⁃time fluorescent quantitative PCR (RT⁃qPCR) was used to detect the expression of miR⁃320 in ileum tissue; Western blotting method was used to detect the expressions of JAK2/STAT3 and NF⁃κB signaling pathway related proteins in ileum. Results: Compared with sham operation group, the pancreas and ileum were severely injured in model group, and the pathological score and ileum cell apoptosis were significantly increased (P<0.05), serum levels of amylase, lipase, TNF⁃ α, and IL⁃1β were significantly increased (P<0.05), the expression of miR⁃320 in ileum tissue was significantly decreased (P<0.05), the ratios of p⁃JAK2/JAK2, p⁃STAT3/STAT3, p⁃p65/p65, and p⁃IκBα/IκBα in ileum tissue were significantly increased (P<0.05). Compared with model group, the pathological damages of pancreas and ileum in agomir miR ⁃ 320 group, AG490 group and PDTC group were reduced, and the pathological score and ileum cell apoptosis were significantly decreased (P<0.05), serum levels of amylase, lipase, TNF ⁃ α, and IL ⁃ 1β were significantly decreased (P<0.05), the expression of miR⁃320 in ileum tissue was significantly increased (P<0.05), the ratios of p⁃JAK2/JAK2, p⁃STAT3/STAT3, p⁃ p65/p65, and p⁃IκBα/IκBα in ileum tissue were significantly decreased (P<0.05). Conclusions: MiR⁃320 can improve the intestinal injury in rats with acute pancreatitis by inhibiting the activation of JAK2/STAT3 and NF⁃κB signaling pathways.
ABSTRACT
Objective To evaluate the effect of sevoflurane postconditioning on autophagy during focal cerebral ischemia-reperfusion (I/R) in rats.Methods Forty-five clean-grade healthy male SpragueDawley rats,weighing 280-350 g,were divided into 3 groups (n=15 each) using a random number table method:sham operation group (S group),cerebral I/R group (I/R group) and sevoflurane postconditioning group (SP group).Focal cerebral I/R injury model was established by Zea-Longa method in chloral hydrate-anesthetized rats.The animals in SP group inhaled 2.4％ sevoflurane for 30 min starting from onset of reperfusion.The expression of autophagy-related proteins LC3 and beclin-1 was detected by Western blot at 2 h of reperfusion.The cerebral cortex was removed for examination of the morphology and number of autophagosomes with an electron microscope.Neurological deficit was assessed and scored at 24 h of reperfusion.Rats were sacrificed at 72 h of reperfusion for determination of the cerebral infarct size.Results Compared with S group,the neurological deficit score was significantly increased,the percentage of cerebral infarct size was increased,LC3Ⅱ/LC3Ⅰ ratio in cerebral cortex was increased,the expression of beclin-1 was up-regulated,and the number of autophagosomes was increased in I/R and SP groups (P＜0.05).Compared with I/R group,the neurological deficit score was significantly decreased,the percentage of cerebral infarct size was decreased,LC3Ⅱ/LC3Ⅰ ratio in cerebral cortex was decreased,the expression of beclin-1 was down-regulated,and the number of autophagosomes was reduced in SP group (P＜0.05).Conclusion Sevoflurane postconditioning mitigates focal cerebral I/R injury through inhibiting autophagy in rats.