Magnolol Pretreatment Prevents Sepsis-Induced Intestinal Dysmotility by Maintaining Functional Interstitial Cells of Caj
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Magnolol Pretreatment Prevents Sepsis-Induced Intestinal Dysmotility by Maintaining Functional Interstitial Cells of Cajal Bin Miao,1 Shuwen Zhang,1,4,5 Hong Wang,1,4,5 Tiecheng Yang,2 Deshan Zhou,3 and Bao-en Wang1
Abstract—The purpose of this study was to investigate the mechanism by which magnolol treatment prevents lipopolysaccharide (LPS)-induced septic dysmotility in mice. Sepsis was induced by intravenous tail vein injection of LPS (4 mg/kg body weight). Animals were divided into three groups: the magnolol-treated septic group, the placebo-treated septic group, and the control group. Intestinal transit and circular smooth muscle contraction were measured 12 h after LPS injection, and immunocytochemisty was performed to study the morphology of interstitial cells of Cajal (ICCs). Stem cell factor (SCF) expression and c-kit phosphorylation were determined by Western blot analysis, and the mRNA levels of inducible NO synthase (iNOS) were determined by RT-PCR. Nitric oxide (NO) content, superoxide dismutase (SOD) activity, and malondialdehyde (MDA) concentration were detected using commercial kits. Intestinal transit and muscular contractility were significantly lower in the LPS-treated group than in the control group. Immunocytochemical experiments showed that the total number of ICCs, and the total and average lengths of the ICC processes were significantly decreased in the LPS-treated group compared with those in the control group. In LPS-treated animals, magnolol pretreatment significantly accelerated intestinal transit, increased circular muscle contraction, and prevented ICC morphology changes. Phosphorylation of c-kit and expression of SCF were significantly downregulated in LPS-treated animals compared with control animals. Magnolol pretreatment prevented sepsis-induced decreases in c-kit phosphorylation and SCF expression in LPS-treated animals. Magnolol pretreatment prevented the sepsis-induced increase in NO concentration, iNOS expression, and MDA concentration, and decrease in SOD activity in LPS-treated animals. Our results suggest that magnolol treatment prevents sepsis-induced intestinal dysmotility by regulating SCF/c-kit and NO signaling to maintain functional ICCs. KEY WORDS: cajal cells; magnolol; motility; SCF/c-kit; signaling pathway; sepsis.
INTRODUCTION
1
Department of Infection, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, China 2 Department of Emergency, Beijing Tiantan Hospital, Capital Medical University, Beijing, 100050, China 3 Department of Histology and embryology, Capital Medical University, Beijing, 100050, China 4 Department of Infection, Beijing Friendship Hospital, Capital Medical University, No. 95 Yong An Road, Beijing, 100050, China 5 To whom correspondence should be addressed at Department of Infection, Beijing Friendship Hospital, Capital Medical University, No. 95 Yong An Road, Beijing, 100050, China. E-mail: [email protected]; E-mail: [email protected]
Sepsis is one of the major causes of mortality and morbidity in severely sick a
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