title: Oxymatrine improves intestinal epithelial barrier function involving NF-κB-mediated signaling pathway in CCl4-induced cirrhotic rats.
abstract: Accumulating evidence suggests that intestinal epithelial barrier dysfunction plays an important role in the pathogenesis of hepatic cirrhosis and its complications such as gastrointestinal injury and hepatic encephalopathy. To date, there is no cure for cirrhosis-associated intestinal mucosal lesion and ulcer. This study aimed to investigate the effect of oxymatrine on intestinal epithelial barrier function and the underlying mechanism in carbon tetrachloride (CCl4)-induced cirrhotic rats. Thirty CCl4-induced cirrhotic rats were randomly divided into treatment group, which received oxymatrine treatment (63 mg/kg), and non-treatment group, which received the same dose of 5% glucose solution (vehicle). The blank group (n = 10 healthy rats) received no treatment. Terminal ileal samples were collected for histopathological examination. The expression level of nuclear factor-κB (NF-κB) p65 in ileal tissue was evaluated by immunohistochemistry. The gene and protein expression levels of tumor necrosis factor-α (TNF-α) and interleukin 6 (IL-6) in ileal tissues were analyzed by reverse-transcriptase polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA), respectively. Additionally, plasma endotoxin level was determined. In comparison to the blank group, a significant alteration in the morphology of intestinal mucosal villi in the non-treatment group was observed. The intestinal mucosal villi were atrophic, shorter, and fractured, and inflammatory cells were infiltrated into the lamina propria and muscular layer. Besides, serious swell of villi and loose structure of mucous membrane were observed. Oxymatrine reversed the CCl4-induced histological changes and restored intestinal barrier integrity. Moreover, oxymatrine reduced the protein expression level of NF-κB p65, TNF-α, and IL-6, which were elevated in the vehicle-treated group. In addition, the serum endotoxin level was significantly decreased after oxymatrine treatment in CCl4-induced cirrhotic rats. The results indicate that oxymatrine improves intestinal barrier function via NF-κB-mediated signaling pathway and may be used as a new protecting agent for cirrhosis-associated intestinal mucosal damage.
authors.affiliation: Department of Gastroenterology, the Affiliated Pingxiang Hospital of Southern Medical University, Pingxiang, Jiangxi, China.
authors.forename: Jian-Bo
authors.initials: JB
authors.lastname: Wen
authors.affiliation: Department of Gastroenterology, the Affiliated Pingxiang Hospital of Southern Medical University, Pingxiang, Jiangxi, China.
authors.forename: Fang-Qing
authors.initials: FQ
authors.lastname: Zhu
authors.affiliation: Department of Gastroenterology, the Affiliated Pingxiang Hospital of Southern Medical University, Pingxiang, Jiangxi, China.
authors.forename: Wei-Guo
authors.initials: WG
authors.lastname: Chen
authors.affiliation: Animal Laboratory, the Affiliated Pingxiang Hospital of Southern Medical University, Pingxiang, Jiangxi, China.
authors.forename: Li-Ping
authors.initials: LP
authors.lastname: Jiang
authors.affiliation: Department of Pharmacology, the Affiliated Pingxiang Hospital of Southern Medical University, Pingxiang, Jiangxi, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Pathology, the Affiliated Pingxiang Hospital of Southern Medical University, Pingxiang, Jiangxi, China.
authors.forename: Zhao-Peng
authors.initials: ZP
authors.lastname: Hu
authors.affiliation: Department of Clinical Laboratory, the Affiliated Pingxiang Hospital of Southern Medical University, Pingxiang, Jiangxi, China.
authors.forename: Yong-Jian
authors.initials: YJ
authors.lastname: Huang
authors.affiliation: Department of Pharmaceutical Science, College of Pharmacy, University of South Florida, Tampa, Florida, United States of America.
authors.forename: Zhi-Wei
authors.initials: ZW
authors.lastname: Zhou
authors.affiliation: Department of Gastroenterology, the Affiliated Pingxiang Hospital of Southern Medical University, Pingxiang, Jiangxi, China.
authors.forename: Gui-Liang
authors.initials: GL
authors.lastname: Wang
authors.affiliation: Department of Gastroenterology, the Affiliated Pingxiang Hospital of Southern Medical University, Pingxiang, Jiangxi, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Lin
authors.affiliation: Department of Pharmaceutical Science, College of Pharmacy, University of South Florida, Tampa, Florida, United States of America.
authors.forename: Shu-Feng
authors.initials: SF
authors.lastname: Zhou
mesh_terms: D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D002251:Carbon Tetrachloride; D004731:Endotoxins / Q000037:antagonists & inhibitors / Q000097:blood; D004797:Enzyme-Linked Immunosorbent Assay; D015870:Gene Expression / Q000187:drug effects; D007150:Immunohistochemistry; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D007422:Intestines / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D008103:Liver Cirrhosis / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology*; D008297:Male; D020011:Protective Agents / Q000494:pharmacology; D011807:Quinolizines / Q000494:pharmacology*; D011897:Random Allocation; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects*; D051996:Transcription Factor RelA / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism; D000093842:Matrines
chemical_list: D000470:Alkaloids; D002251:Carbon Tetrachloride; D004731:Endotoxins; D015850:Interleukin-6; D020011:Protective Agents; D011807:Quinolizines; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha; C037573:oxymatrine; D000093842:Matrines