Berberine protects steatotic donor undergoing liver transplantation via inhibiting endoplasmic reticulum stress-mediated reticulophagy
Berberine protects steatotic donor undergoing liver transplantation via inhibiting endoplasmic reticulum stress-mediated reticulophagy
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小檗碱通过抑制内质网应激介导的网状吞噬来保护接受肝移植的脂肪变性供体
DOI：
10.1177/1535370219878651
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发表时间：
2019-09
影响因子：
3.2
通讯作者：
Du Hongyin
中科院分区：
文献类型：
--
作者：
Sheng Mingwei;Zhang Nan;Wu Man;Zhang Xinyue;Ding Yijie;Lin Yuanbang;Yu Wenli;Wang Shusen;Du Hongyin
脂肪肝更容易受到缺血/再灌注损伤，并增加肝移植后原发性移植物无功能的风险。小檗碱的保护作用已在各种肝脏病理模型中描述。然而，黄连素是否在接受肝移植的脂肪变性供体中发挥其有益作用尚不清楚。在本研究中，雄性Wistar大鼠喂饲高脂饲料（HFD）12周，以诱导中度脂肪肝。然后建立了原位肝移植模型。术前1周给予黄连素200 mg/kg/d灌胃。Thapsigargin（TG）0.2mg/kg于肝移植前24 h静脉注射。通过生化或组织病理学分析检测肝功能、氧化应激和炎性细胞因子。透射电镜观察自噬体和内质网的形态。Western blot检测CHOP、BIP、PERK磷酸化、LC 3-II/I、Beclin-1和p62的表达。免疫荧光显微镜下观察内质网标志物（KDEL）和自噬蛋白（LC 3B）的共定位。用免疫组化法检测网状细胞吞噬标志物（FAM 134 B）的表达。与HFD + LT组相比，小檗碱可减轻肝细胞损伤，降低氧化应激水平和炎性细胞因子释放。同时，小檗碱抑制内质网应激参数和自噬相关蛋白的表达。此外，内质网标记物和LC 3B的共定位在HFD + BBR + LT组中也减少。小檗碱下调FAM 134 B的表达。TG逆转了小檗碱的有益作用。我们的研究表明，黄连素通过抑制内质网应激介导的网状吞噬作用对接受移植的脂肪变性肝脏产生保护作用。黄连素是从传统中药植物中分离出来的，对炎症、腹泻和糖尿病有显著的治疗潜力。但是，BBR对肝移植后脂肪变性移植物的益处仍然知之甚少。我们的研究结果可能有助于解释黄连素在保护接受移植的脂肪肝的机制，并提供有利的见解，黄连素有可能作为一个合适的候选人，通过抑制ER应激介导的网状吞噬，以防止脂肪肝肝移植后的肝损伤。
Steatotic livers are more susceptible to ischemia/reperfusion injury, and increase the risk of primary graft non-function after liver transplantation. The protective effects of berberine have been described in various liver pathological models. However, it is unknown if berberine exerts its beneficial action in steatotic donors undergoing liver transplantation. In the present study, male Wistar rats were fed with high-fat diet (HFD) for 12 weeks to induce moderate steatotic liver. Then orthotropic liver transplantation was constructed. Berberine (200 mg/kg/d) was given intragastrically one week before liver transplantation. Thapsigargin (TG) (0.2 mg/kg) was administrated intravenously 24 h before liver transplantation. Liver function, oxidative stress, and inflammatory cytokine were detected by biochemical or histopathological analysis. The morphology of autophagosomes and endoplasmic reticulum (ER) was observed by transmission electron microscopy. The expression of CHOP, BIP, the phosphorylation of PERK, LC3-II/I, Beclin-1, and p62 were determined by Western blot assay. The co-localization of endoplasmic reticulum marker (KDEL) and autophagic protein (LC3B) was analyzed by immunofluorescence microscopy. The level of reticulophagy hallmark (FAM134B) was determined by immunohistochemistry. Compared with HFD + LT group, berberine ameliorated hepatocellular damage, decreased the oxidative stress level and inflammatory cytokine release. Simultaneously, berberine inhibited the expression of both endoplasmic reticulum stress parameters and autophagy-related proteins. Additionally, the co-localization of endoplasmic reticulum marker and LC3B was also reduced in HFD + BBR + LT group. berberine down-regulated the level of FAM134B. TG reversed the beneficial effects of berberine. Our study revealed that berberine exerts protective effects on steatotic livers undergoing transplantation by inhibiting endoplasmic reticulum stress-mediated reticulophagy. Impact statement Berberine is isolated from traditional Chinese medicine plants and has dramatically therapeutic potential against inflammation, diarrhea, and diabetes. But the benefits of BBR on steatotic grafts after liver transplantation remain poorly understood. Our findings might help explain the mechanism of berberine in protecting steatotic livers undergoing transplantation and give advantageous insights that berberine has potential as a suitable candidate for preventing hepatic injury after steatotic liver transplantation by inhibiting ER stress-mediated reticulophagy.
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影响因子：
4.7
作者：
Ivankovic D;Chau KY;Schapira AH;Gegg ME
通讯作者：
Gegg ME
DOI：
10.18632/aging.101083
发表时间：
2016-10-24
期刊：
Aging
影响因子：
--
作者：
Ghosh AK;Mau T;O'Brien M;Garg S;Yung R
通讯作者：
Yung R
影响因子：
1.5
作者：
Ramachandran S;Liaw JM;Jia J;Glasgow SC;Liu W;Csontos K;Upadhya GA;Mohanakumar T;Chapman WC
通讯作者：
Chapman WC
影响因子：
13.3
作者：
Chi, Hsiang-Cheng;Chen, Shen-Liang;Lin, Kwang-Huei
通讯作者：
Lin, Kwang-Huei
影响因子：
13.3
作者：
Bartlett, Bryan J.;Isakson, Pauline;Finley, Kim D.
通讯作者：
Finley, Kim D.