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Study on improvement mechanism of caudatin on liver injury in rats
- ZHONGGUO YAOFANG Vol. 34, Issue 5, Pages: 531-536(2023)
- 作者机构：
1.南京中医药大学第三临床医学院，南京 210028
2.南京中医药大学附属连云港市中医院药学部，江苏 连云港 222002
3.中国中医科学院江苏分院/江苏省中医药研究院国家中医药管理局中药口服释药系统重点研究室，南京 210028
4.南京中医药大学附属中西医结合医院肿瘤科，南京 210028
- 作者简介：
- 基金信息：
DOI：10.6039/j.issn.1001-0408.2023.05.04
CLC： R965Published：15 March 2023，
Received：18 September 2022，
Revised：04 February 2023，
扫 描 看 全 文
常志惠,补阳,刘茜等.告达庭对大鼠肝损伤的改善作用机制研究 Δ[J].中国药房,2023,34(05):531-536.
CHANG Zhihui,BU Yang,LIU Qian,et al.Study on improvement mechanism of caudatin on liver injury in rats[J].ZHONGGUO YAOFANG,2023,34(05):531-536.
常志惠,补阳,刘茜等.告达庭对大鼠肝损伤的改善作用机制研究 Δ[J].中国药房,2023,34(05):531-536. DOI： 10.6039/j.issn.1001-0408.2023.05.04.
CHANG Zhihui,BU Yang,LIU Qian,et al.Study on improvement mechanism of caudatin on liver injury in rats[J].ZHONGGUO YAOFANG,2023,34(05):531-536. DOI： 10.6039/j.issn.1001-0408.2023.05.04.
摘要
目的
2
探讨告达庭改善大鼠肝损伤的作用机制。
方法
2
将SD大鼠随机分为空白组、模型组和告达庭低、高剂量组（25、50 mg/kg），每组6只。采用腹腔注射（每周3次，连续8周）二乙基亚硝胺（DEN）复制大鼠肝损伤模型。造模第5周，大鼠灌胃相应药物或0.5%羧甲基纤维素钠，连续4周。检测大鼠血清中肝功能指标[丙氨酸转氨酶（ALT）、天冬氨酸转氨酶（AST）、总蛋白（TP）和总胆红素（TBI）]及炎症因子[白细胞介素6（IL-6）、肿瘤坏死因子α（TNF-α）、IL-1β]水平，观察大鼠肝脏组织病理学形态变化，检测肝脏组织中核因子κB（NF-κB）、78 kDa葡糖调节蛋白（Grp78）蛋白阳性表达水平，检测肝脏组织中内质网应激相关蛋白Grp78、C/EBP同源蛋白（CHOP）、转录激活因子6（ATF6）、肌醇需求激酶1α（IRE1α）的表达水平和蛋白激酶R样内质网激酶（PERK）磷酸化水平。
结果
2
与空白组比较，模型组大鼠血清中ALT、AST、TBI、IL-6、TNF-α、IL-1β水平和肝脏组织中NF-κB、Grp78蛋白阳性表达水平以及Grp78、CHOP、ATF6 、IRE1α蛋白表达水平和PERK蛋白磷酸化水平均显著升高（
P
＜0.05），血清中TP水平显著降低（
P
＜0.05）；肝小叶结构紊乱，肝细胞肿胀，细胞间分界不明显，且伴随炎症细胞浸润。与模型组相比，告达庭各剂量组大鼠上述大部分指标显著逆转（
P
＜0.05）；肝小叶结构较完整清晰，细胞排列趋整齐，炎症细胞浸润也有所减少。
结论
2
告达庭对DEN所致大鼠肝损伤具有明显的改善作用，其作用机制可能与抑制内质网应激和炎症反应有关。
Abstract
OBJECTIVE
2
To investigate the improvement mechanism of caudatin on liver injury of rats.
METHODS
2
SD rats were randomly divided into blank group， model group， caudatin low-dose and high-dose groups （25， 50 mg/kg）， with 6 rats in each group. Diethylnitrosamine （DEN） was injected intraperitoneally three times per week for eight weeks to establish liver injury model of rats. At 5th week of modeling， the rats received relevant medicine or 0.5% sodium carboxymethylcellulose intragastrically for 4 weeks. The levels of liver function indexes [alanine transaminase （ALT）， aspartate transaminase （AST）， total protein （TP） and total bilirubin （TBI）] and inflammatory factors [interleukin （IL-6）， tumor necrosis factor α （TNF-α）， IL-1β] in serum were detected； the histopathological morphological changes of rat liver were observed； the positive protein expressions of nuclear factor κB （NF-κB） and 78 kDa glucose regulatory protein （Grp78） in liver tissue were also determined； the expressions of endoplasmic reticulum stress-related protein Grp78， C/EBP homologous protein （CHOP）， activating transcription factor 6 （ATF6） and inositol requiring enzyme 1α （IRE1α） and the level of protein kinase R-like endoplasmic reticulum kinase （PERK） in liver tissue were detected.
RESULTS
2
Compared with blank group， serum levels of ALT， AST， TBI， IL-6， TNF-α and IL-1β and positive expressions of NF-κB and Grp78 in liver tissue as well as protein expressions of Grp78， CHOP， ATF6 and IRE1α， PERK protein phosphorylation level were all increased significantly in model group （
P
＜0.05）， while the serum level of TP was decreased significantly （
P
＜0.05）. The disordered structure of liver lobule， swollen liver cells， unclear intercellular boundary were observed and accompanied by inflammatory cell infiltration. Compared with model group， most of the above indexes were significantly reversed in caudatin groups （
P
＜0.05）； the structure of hepatic lobule was relatively complete and clear， the cells were arranged orderly， and the infiltration of inflammatory cells was also reduced.
CONCLUSIONS
2
Caudatin has a significant improvement effect against DEN-induced liver injury in rats， the mechanism of which may be associated with inhibiting endoplasmic reticulum stress and inflammatory reaction.
关键词
内质网应激告达庭炎症肝损伤二乙基亚硝胺
Keywords
caudatininflammationliver injurydiethylnitrosamine
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