Effects of Carbon Tetrachloride-induced Acute Liver Injury on Cardiac Pathological Changes in a Rat Model

doi:10.12300/j.issn.1674-5817.2021.033

Abstract

Abstract: Objective To investigate the effects of carbon tetrachloride (CCl₄) on cardiac function and morphology in rats with acute liver injury. Methods Rat models of acute liver injury were established by intraperitoneal injection with different concentrations of CCl₄, while an equal volume of vegetable oil was injected intraperitoneally as a control group. Electrocardiogram (ECG) was performed at 24 and 48 hours after inducted by CCl₄, and the animals were sacrificed after blood collection from the abdominal aorta. The levels of serum alanine aminotransferase (ALT) and cardiac troponinⅠ(CTNⅠ) were measured by an enzyme-linked immunosorbent assay. Liver and heart tissues were sectioned and stained with hematoxylin-eosin (HE) and the pathological changes were observed by optical microscopy. The levels of malondialdehyde (MDA), superoxide dismutase (SOD), and creatine kinase (CK) in myocardial tissues were measured by visible light spectrophotometer. Results The changes in serum ALT level and liver morphological in the model groups proved that the acute liver injury model induced by CCl₄ was successfully established, and the degree of liver injury was dose-dependent. The ECG of the model groups revealed electrophysiological changes, such as ST-segment elevation, T-wave sharp, and Q-T interval prolongation in different degrees. HE staining showed that obvious pathological changes in the heart tissue, and the degree of inflammatory reaction, edema and necrosis of myocardial cells gradually aggravated with the increase of CCl₄ injection concentration. Serum CTN Ⅰlevels were significantly increased (P<0.01), CK and MDA levels in the myocardial tissue were significantly increased (P<0.05), while SOD levels in the myocardial tissue were significantly decreased (P<0.05), and the changes in various indexes were more significant in the high concentration CCl₄ group and 48 h after induction by CCl₄. Conclusion CCl₄ can induce cardiac function and morphological changes in rats with acute liver injury, and the degree of myocardial injury is dose- and time-dependent.

Key words: CCl₄, Acute liver injury, Myocardial lesions, Rat

CLC Number:

R363
Q95-33

ZHANG Lili, WAN Xin, JI Jingquan, LI Ting, FAN Yimin, LI Baohong, TIAN Shuaiyan. Effects of Carbon Tetrachloride-induced Acute Liver Injury on Cardiac Pathological Changes in a Rat Model[J]. Laboratory Animal and Comparative Medicine, 2021, 41(6): 486-492.

Figures/Tables 6

References

[1] 韩冬. 甲苯急性染毒对小鼠心脏、肝脏影响的初步研究[D]. 太原: 山西医科大学, 2009.
[2] LEE G H, LEE H Y, CHOI M K, et al.Protective effect of Curcuma longa L. extract on CCl₄-induced acute hepatic stress[J]. BMC Res Notes, 2017, 10(1):1-9. DOI:10.1186/s13104-017-2409-z.
[3] 朱安妮, 李蕊, 刘三海, 等. 四氯化碳诱导小鼠急性肝损伤模型的建立和优化[J]. 中国肝脏病杂志(电子版), 2014, 6(1):27-31. DOI:10.3969/j.issn.1674-7380.2014.01.007.
[4] DONG S, CHEN Q L, SONG Y N, et al.Mechanisms of CCl₄-induced liver fibrosis with combined transcriptomic and proteomic analysis[J]. J Toxicol Sci, 2016, 41(4):561-572. DOI:10.2131/jts.41.561.
[5] 刘赴平, 师玲玲. 四氯化碳造成急性肝损伤大鼠模型的实验研究[J]. 中国输血杂志, 2012, 25(5):446-448. DOI:10.13303/j.cjbt.issn.1004-549x.2012.05.025.
[6] 班跃松. EC-SOD在大鼠肝缺血再灌注损伤模型心肌内的表达变化[D]. 石家庄: 河北医科大学, 2016.
[7] SHARMA P, SHARMA B C.Lactulose for minimal hepatic encephalopathy in patients with extrahepatic portal vein obstruction[J]. Saudi J Gastroenterol, 2012, 18(3):168-172. DOI:10.4103/1319-3767.96448.
[8] VENKAT D, VENKAT K K.Hepatorenal syndrome[J]. South Med J, 2010, 103(7):654-661. DOI:10.1097/SMJ.0b013e3181e07751.
[9] 任晓彦, 万鑫, 杨颖, 等. 不同浓度CCl₄ 对大鼠肾功能的影响研究[J]. 长治医学院学报, 2019, 33(4):248-251. DOI.10.3969/j.issn.1006-0588.2019.04.003.
[10] 魏晓光, 郭辉, 陈永珍, 等. 腹腔注射四氯化碳建立大鼠肝纤维化模型[J]. 实验室研究与探索, 2015, 34(11):34-37. DOI:10.3969/j.issn.1006-7167.2015.11.010.
[11] 孙家昌, 孙妩弋, 厉歆然, 等. 不同浓度四氯化碳诱导小鼠肝纤维化模型的比较[J]. 实验动物与比较医学, 2018(4):255-260.
[12] OTRUBOVÁ O, TURECKÝ L, ULIČNÁ O, et al. Therapeutic effects of N-acetyl-L-cysteine on liver damage induced by long-term CCl₄ administration[J]. Gen Physiol Biophys, 2018, 37(1):23-31. DOI:10.4149/gpb_2017016.
[13] 闻名, 卢瑾, 谢元林. 2019冠状病毒病患者合并肝损伤的临床特点[J]. 中南大学(医学版), 2020, 45(5):555-559. DOI:10.11817/j.issn.1672-7347.2020.200225.
[14] XIONG X, REN Y, CUI Y, et al.Obeticholic acid protects mice against lipopolysaccharide-induced liver injury and inflammation[J]. Biomed Pharmacother, 2017, 96:1292-1298. DOI:10.1016/j.biopha.2017.11.083.
[15] MASHHADI S N Y, ASKARI V R, GHORANI V, et al. The effect of Portulaca oleracea and α-linolenic acid on oxidant/antioxidant biomarkers of human peripheral blood mononuclear cells[J]. Indian J Pharmacol, 2018, 50(4):177-184. DOI:10.4103/ijp.IJP_737_16.
[16] BLANKENBERG S, WITTLINGER T, NOWAK B, et al.Troponins as biomarkers for myocardial injury and myocardial infarction[J]. Herz, 2019, 44(1):4-9. DOI:10.1007/s00059-019-4783-x.
[17] 甄军海, 李莉, 严静. 脓毒症心肌损伤生物标志物的研究进展[J]. 中华危重病急救医学, 2018, 30(7):699-702. DOI:10.3760/cma.j.issn.2095-4352.2018.07.017.
[18] PARADIES G, PARADIES V, RUGGIERO F M, et al.Mitochondrial bioenergetics and cardiolipin alterations in myocardial ischemia-reperfusion injury: implications for pharmacological cardioprotection[J]. Am J Physiol Heart Circ Physiol, 2018, 315(5): H1341-H1352. DOI:10.1152/ajpheart.00028.2018.
[19] 邹瑛, 宋金春, 马俊玲. 复方当归注射液对异丙肾上腺素诱导大鼠心肌缺血的保护作用[J]. 中国药师, 2007, 10(1):6-8. DOI:10.3969/j.issn.1008-049X.2007.01.002.
[20] LIU X W, LU M K, ZHONG H T, et al.Panax notoginseng saponins attenuate myocardial ischemia-reperfusion injury through the HIF-1α/BNIP₃ pathway of autophagy[J]. J Cardiovasc Pharmacol, 2019, 73(2):92-99. DOI:10.1097/fjc.0000000000000640.
[21] 牛丹丹, 刘振, 李方方. miR-146 a-5 p通过调控Notch2表达对心肌缺血再灌注模型大鼠心肌损伤的影响[J]. 中国免疫学杂志, 2020, 36(5):530-537, 554. DOI:10.3969/j.issn.1000-484X.2020.05.004.