The Inhibiting Effect Of OAT β-glucan On Lipopolysaccharide-induced Nonalcoholic Steatohepatitis In Mice

As part of the spectrum of nonalcoholic fatty liver disease, the incidence of nonalcoholicsteatohepatitis (NASH) is high. However, the pathogenesis of NASH has not been as yetclearly elaborated and there have been very limited advances in the treatmentand prevention of NASH. Although possessing the physiological effect of reducing therisk of cardiovascular disease, the inhibiting effect of oat β-glucan on NASH has not beenreported. The aim of the present work was to establish a lipopolysaccharide (LPS)injection-induced mouse model of NASH and to evaluate the potential inhibiting effect of oatβ-glucan. The purity of oat β-glucan used in this study was81.94%(w/w) and the molecularweight was152kDa.40C57BL/6mice were purchased and then randomly divided into fivegroups by eight mice. Lipopolysaccharide (LPS)-injected group was intraperitoneally injectedphysiological saline-dissolved LPS by1.5mg/kg body weight per day and supplied the SPFfeed added with no oat β-glucan. After6weeks, we evaluate whether LPS could induceNASH in mice by the measurements of serum biochemical indexes, liver physicochemicalindexes and proinflammatory cytokines as well as the observation of liver histopathologicalchanges. Control group (n=6) was injected the same dose of physiological saline comparedwith LPS-injected group per day for6weeks and supplied the SPF feed added with no oatβ-glucan. LPS+Low oat β-glucan group, LPS+Moderate oat β-glucan group and LPS+Highoat β-glucan group were each intraperitoneally injected physiological saline-dissolved LPS by1.5mg/kg body weight per day and were supplied the SPF feed added with1%,5%and10%oat β-glucan respectively. After6weeks of intraperitoneal injection of LPS, we measured theNASH-related indexes and observed liver histopathological changes to investigate theinhibiting effect of oat β-glucan on LPS-induced nonalcoholic steatohepatitis in mice.The main results were as follows:(1) Intraperitoneal injection of LPS by1.5mg/kg body weight per day for6weeks couldinduce the increase of ALT and AST levels (P<0.05), augment liver index and the content ofliver triglyceride (P<0.05), increase the levels of TNF-α, IL-6(P<0.05), IL-1β (P<0.05) andMDA (P<0.05) in liver as well as indistinctively decreasing SOD activity. Histologicevaluation revealed evidence of hepatic steatosis, inflammation, and mild necrosis in LPS-treated mice. These results indicated that intraperitoneal injection of LPS by1.5mg/kgbody weight per day for6weeks could induce NASH in mice.(2) Oat β-glucan could improve endotoxemia, insulin resistance and sugar intolerance,decrease intestinal permeability, restrain body weight gain and decrease the level of serumtotal cholesterol in mice intraperitoneally injected by LPS for6weeks, although there did notexist a dose-effect relationship between oat β-glucan content and the influence on the growingand serum biochemical indexes of LPS-injected mice.(3) Dietary supplementation of oat β-glucan improved abnormal aminotransferaseactivity and hepatic superoxide dismutase activity; inhibited the increase of hepaticproinflammatory cytokines (tumor necrosis factor-α, interleukin-6, interleukin-1β),triglyceride and malonyl dialdehyde level. Histologic evaluation revealed that oat β-glucanadded to SPF diet could improve hepatic steatosis, inflammation and necrosis. These resultsindicated that oat β-glucan could effectively inhibit LPS-induced nonalcoholic steatohepatitisin mice, although a dose-dependent effect was not observed.