{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,20]],"date-time":"2026-01-20T09:21:42Z","timestamp":1768900902671,"version":"3.49.0"},"reference-count":35,"publisher":"Bentham Science Publishers Ltd.","issue":"9","content-domain":{"domain":["eurekaselect.com"],"crossmark-restriction":true},"short-container-title":["CMM"],"published-print":{"date-parts":[[2021,1,19]]},"abstract":"<jats:sec>\n<jats:title>Objectives:<\/jats:title>\n<jats:p>This study was designed to investigate the effects of carvedilol\non the expression of TLR4 and its downstream signaling pathway in the liver tissues of\nrats with cholestatic liver fibrosis and provide experimental evidence for clinical\ntreatment of liver fibrosis with carvedilol.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Methods:<\/jats:title>\n<jats:p> A total of fifty male Sprague Dawley rats were randomly divided into five\ngroups (10 rats per group): sham operation (SHAM) control group, bile duct ligation\n(BDL) model group, low-dose carvedilol treatment group (0.1mg\u00b7kg<jats:sup>-1<\/jats:sup>\u00b7d<jats:sup>-1<\/jats:sup>), medium-dose\ncarvedilol treatment group (1mg\u00b7kg<jats:sup>-1<\/jats:sup>\u00b7d<jats:sup>-1<\/jats:sup>), and high-dose carvedilol treatment group\n(10mg\u00b7kg<jats:sup>-1<\/jats:sup>\u00b7d<jats:sup>-1<\/jats:sup>). Rat hepatic fibrosis model was established by applying BDL. Forty-eight\nhours after the operation, carvedilol was administered twice a day. The blood and liver\nwere simultaneously collected under the aseptic condition for further detection in two\nweeks after the operation. The alanine aminotransferase (ALT), aspartate\naminotransferase (AST), total bilirubin (TBil) and albumin (Alb) in serum were measured.\nHE and Masson staining were used to determine hepatic fibrosis degree. Hydroxyproline\nassay was employed to detect liver collagen synthesis. Western Blot was used to\nmeasure the expression of TLR4, NF-\u03baB p65 and \u03b2-arrestin2 protein. Quantitative\nanalysis of TLR4, MyD88, TNF-\u03b1 and IL-6 mRNA was performed by Realtime-PCR.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Results:<\/jats:title>\n<jats:p>Compared with the SHAM group, the BDL group showed obvious liver injury,\nincreased levels of inflammatory factors, and continued progression of liver fibrosis. The\nabove changes in the BDL group were alleviated in the carvedilol treatment groups. The\nimprovement effects augmented as dosages increased. In addition, compared with the\nBDL group, the reduction of the expressions of TLR4, MyD88 and NF-\u03baB p65 in liver\ntissues and the increase of the expression of \u03b2 -arrestin2 in the high-dose carvedilol\ngroup were more significant.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Conclusions:<\/jats:title>\n<jats:p>Carvedilol can reduce the release of inflammatory mediators by downregulating\nTLR4 expression and inhibiting its downstream signaling pathway, thus\nplaying a potential therapeutic role in cholestatic liver fibrosis.<\/jats:p>\n<\/jats:sec>","DOI":"10.2174\/1566524020666200220130705","type":"journal-article","created":{"date-parts":[[2020,2,20]],"date-time":"2020-02-20T15:23:14Z","timestamp":1582212194000},"page":"708-716","update-policy":"https:\/\/doi.org\/10.2174\/bsp_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Effects of Carvedilol on the Expression of TLR4 and its Downstream Signaling Pathway in the Liver Tissues of Rats with Cholestatic Liver Fibrosis"],"prefix":"10.2174","volume":"20","author":[{"given":"Xiaopeng","family":"Tian","sequence":"first","affiliation":[{"name":"Department of Gastroenterology, Xingtai People\u2019s Hospital, Xingtai, Hebei 054000, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huimin","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Xingtai People\u2019s Hospital, Xingtai, Hebei 054000, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zengcai","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Xingtai People\u2019s Hospital, Xingtai, Hebei 054000, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"965","reference":[{"key":"ref=1","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1016\/j.mam.2018.09.002","volume":"65","author":"Parola M.","year":"2019","unstructured":"Parola M.; Pinzani M.; Liver fibrosis: Pathophysiology, pathogenetic targets and clinical issues. 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