Changes of Expressions of Intestinal Mucosal Tight Junction Proteins ZO-1 and Occludin in Rats with Acute Intrahepatic Cholestasis

Objective To study the changes of expressions of intestinal mucosal tight junction proteins ZO-1 and Occludin in rats with acute intrahepatic cholestasis,and explore its mechanisms.Methods Forty SD rats aged 21 days were randomly divided into control group(n=10) and model group(n=30).A single dose(50 mg.kg-1) of α-naphthylisothiocyanate was administered by gavage to each experimental rats to induce acute intrahepatic cholestasis in model group.Rats in control group only administered with caster oil by gavage.At 24 hours,48 hours and 72 hours after gavage,immunohistochemistry and Western blot techniques were used to examine the distribution and expression of tight junction proteins(ZO-1,Occludin),and the results of Western blot were quantitatively analyzed by image analytical system.Results ZO-1 and Occludin were localized along the apical region of the lateral plasma membrane representing the region of tight junctions in surface and crypt epithelial cells.Compared with control group,the positive stainings of ZO-1 and Occludin in model group at 24 hours after gavage were decreased,the decrease was most obviously at 48 hours,and partly recovered at 72 hours.Western blot demonstrated consistent and significant reduction with immunohistochemistry.The expressions of ZO-1 and Occludin in model group were 0.129 4±0.048 1 and 0.195 0±0.044 1 at 24 hours,0.039 5±0.009 5 and 0.013 7±0.009 2 at 48 hours,0.202 4±0.049 8 and 0.149 4±0.035 5 at 72 hours,which were significantly lower than those in control group(ZO-1:0.288 7±0.023 7,Occludin:0.426 6±0.067 0)(Pa0.01).Conclusions Acute intrahepatic cholestasis induces the abnormal distribution of tight junction proteins and the alteration of their quantity,which affects the intestinal barrier integrity,resulting in impaired barrier function.