Tian Xiaopeng, Zhao Huimin, Guo Zengcai
Gastroenterology , Xingtai Peoples Hospital, China.
Xingtai Peoples Hospital.
Rev Esp Enferm Dig. 2020 Nov 17. doi: 10.17235/reed.2020.6075/2018.
Ahead of Print article withdrawn by publisher.
This study was designed to investigate the effects of carvedilol on the expression of TLR4 and its downstream signaling pathway in liver tissue of rats with cholestatic liver fibrosis, and provided experimental evidence for clinical treatment of liver fibrosis with carvedilol.?
A total of fifty male Sprague Dawley rats were randomly divided into five groups (10 rats per group): sham surgery control group, bile duct ligation (BDL) model group, low-dose carvedilol treatment group (0.1mgkg-1d-1), medium-dose carvedilol treatment group (1mgkg-1d-1), high-dose carvedilol treatment group (10mgkg-1d-1). Rat hepatic fibrosis model was established by applying BDL. Forty-eight hours after the operation, carvedilol was administered twice a day. The blood and liver were simultaneously collected under the aseptic condition for further detection in two weeks after operation.?
Compared with the sham group, the BDL group showed obvious liver injury, increased levels of inflammatory factors, and continued progression of liver fibrosis. Carvedilol could alleviate the above changes. The improvement effects were augmenting as dosages increasing. In addition, compared with the BDL group, carvedilol can reduce the expressions of TLR4, MyD88 and NF-?B p65 in liver tissue and increase the expression of ?-arrestin2, and the effect in the high dose group was more obvious.
Carvedilol can reduce the release of inflammatory mediators by down-regulating TLR4 expression and inhibiting its downstream signaling pathway, thus playing a therapeutic role in cholestatic liver fibrosis.
出版前文章被出版商撤回。
本研究旨在探讨卡维地洛对胆汁淤积性肝纤维化大鼠肝组织中TLR4及其下游信号通路表达的影响，为卡维地洛临床治疗肝纤维化提供实验依据。
将50只雄性Sprague Dawley大鼠随机分为5组（每组10只）：假手术对照组、胆管结扎（BDL）模型组、低剂量卡维地洛治疗组（0.1mg/kg·d-1）、中剂量卡维地洛治疗组（1mg/kg·d-1）、高剂量卡维地洛治疗组（10mg/kg·d-1）。采用BDL法建立大鼠肝纤维化模型。术后48小时，每天给大鼠灌胃卡维地洛2次。术后2周，在无菌条件下同时采集血液和肝脏进行进一步检测。
与假手术组相比，BDL组肝损伤明显，炎症因子水平升高，肝纤维化持续进展。卡维地洛可减轻上述变化，且随着剂量增加，改善效果增强。此外，与BDL组相比，卡维地洛可降低肝组织中TLR4、MyD88和NF-κB p65的表达，增加β-arrestin2的表达，高剂量组效果更明显。
卡维地洛可通过下调TLR4表达并抑制其下游信号通路，减少炎症介质释放，从而对胆汁淤积性肝纤维化发挥治疗作用。
