切换至 "中华医学电子期刊资源库"

中华临床医师杂志(电子版) ›› 2020, Vol. 14 ›› Issue (11) : 922 -925. doi: 10.3877/cma.j.issn.1674-0785.2020.11.014

所属专题: 文献

基础研究

异甘草酸镁对紫杉醇致大鼠肝损伤的防治作用及其对血清IL-6、IL-10、TNF-α的影响
赖雪莹1, 刘斌2, 胡学琴3, 陈浩军1,()   
  1. 1. 511400 广州,广州市番禺区中心医院消化中心三区
    2. 510515 广州,南方医科大学南方医院药学部
    3. 511400 广州,广州市番禺区妇幼保健院儿科
  • 收稿日期:2020-08-03 出版日期:2020-11-15
  • 通信作者: 陈浩军
  • 基金资助:
    广州市卫生健康科技一般引导项目(20201A011116)

Therapeutic effect of magnesium isoglycyrrhizinate on liver injury induced by paclitaxel and its effect on serum IL-6, IL-10 and TNF-α

Xueying Lai1, Bin Liu2, Xueqin Hu3, Haojun Chen1,()   

  1. 1. The Third Department of Digestion Center, Panyu Central Hospital, Guangzhou 511400, China
    2. Department of Pharmacy, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China
    3. Department of Pediatrics, Guangzhou Panyu District Maternal and Child Health Hospital, Guangzhou 511400, China
  • Received:2020-08-03 Published:2020-11-15
  • Corresponding author: Haojun Chen
引用本文:

赖雪莹, 刘斌, 胡学琴, 陈浩军. 异甘草酸镁对紫杉醇致大鼠肝损伤的防治作用及其对血清IL-6、IL-10、TNF-α的影响[J/OL]. 中华临床医师杂志(电子版), 2020, 14(11): 922-925.

Xueying Lai, Bin Liu, Xueqin Hu, Haojun Chen. Therapeutic effect of magnesium isoglycyrrhizinate on liver injury induced by paclitaxel and its effect on serum IL-6, IL-10 and TNF-α[J/OL]. Chinese Journal of Clinicians(Electronic Edition), 2020, 14(11): 922-925.

目的

观察异甘草酸镁(MgIG)对紫杉醇(PTX)致大鼠急性肝损伤的防治作用及对其体内IL-6、IL-10、TNF-α水平的影响。

方法

大鼠50只,采用随机数字表法分成空白组、模型组、MgIG 低剂量组(6.25 mg/kg)、中剂量组(12.5 mg/kg)和高剂量组(25 mg/kg)。MgIG 3个剂量组腹腔注射给药,空白组和模型组给予等体积生理盐水,1次/d,连续腹腔注射给药14 d。除对照组外,其余各组于实验第5天腹腔注射PTX 8 mg/kg建立大鼠肝损伤模型。最后一次给药后24 h,处死大鼠取材,分离血清检测谷丙转氨酶(ALT)、谷草转氨酶(AST)值;ELISA 法检测白介素(IL)-6、IL-10、肿瘤坏死因子(TNF)-α的水平变化;采用HE染色观察各组大鼠肝脏组织病理学改变。

结果

与模型组比较,MgIG低、中、高剂量组大鼠血清ALT[(43.97±7.18)、(42.17±7.67)、(33.63±4.09)U/L vs (52.33±5.63)U/L]和AST[(78.06±5.07)、(75.83±6.45)、(70.40±7.12)U/L vs (86.84±8.72)U/L]水平降低(P<0.05,P<0.01,P<0.001);与模型组比较,MgIG低、中、高剂量组IL-6[(239.97±13.74)、(236.14±26.12)、(191.34±15.83)ng/L vs (261.02±10.88)ng/L]水平降低(P<0.05,P<0.01,P<0.001),MgIG中、高剂量组IL-10[(30.25±5.25)、(37.06±7.73)pg/ml vs (23.64±2.09)pg/ml]水平升高(P<0.05,P<0.001),TNF-α[(70.83±5.91)、(57.83±8.20)ng/L vs (85.27±6.54)ng/L]水平降低(P<0.01,P<0.001)。光镜下MgIG 3个剂量组的炎症程度较模型组减轻,并随着剂量增加而减轻程度增加,呈剂量药效关系。

结论

MgIG通过改变大鼠血清促炎因子的水平,并且改善大鼠肝脏病理组织损伤程度,进而对PTX所致大鼠肝损伤起保护作用。

Objective

To observe the therapeutic effects of magnesium isoglycyrrhizinate (MgIG) on acute liver injury induced by paclitaxel and its effect on the levels of IL-6, IL-10 and TNF-α in rats.

Methods

Using a random number table method, 50 rats were divided into blank group, model group, MgIG low-dose group (6.25 mg/kg), middle-dose group (12.5 mg/kg) and high-dose group (25 mg/kg). MgIG was given by intraperitoneal injection in 3 dose groups, and the blank group and model group were given equal volume of normal saline, once daily, for 14 days. Except for the control group, the other 4 groups were intraperitoneally injected with paclitaxel 8 mg/kg on the 5th day to establish a rat liver injury model. Rats were sacrificed 24 h after the last administration. Serum was collected to detect alanine aminotransferase (ALT) and aspartate aminotransferase (AST) values. ELISA mathod was used to detect interleukin-6 (IL-6), interleukin-10 (IL-10) and tumor necrosis factor-α (TNF-α) level. HE staining was used to observe histopathological changes in the liver of rats in each group.

Results

The ALT levels of the low, medium and high doses group[(43.97±7.18), (42.17±7.67), (33.63±4.09) U/L] and AST levels [(78.06±5.07), (75.83±6.45), (70.40±7.12) U/L] were significantly lower than those [(52.33±5.63), (86.84±8.72) U/L] of the model group (P<0.05, P<0.01 or P<0.001). IL-6 levels in low, medium and high dose groups [(239.97±13.74), (236.14±26.12), (191.34±15.83) ng/L] and IL-10 levels in middle and high dose groups [(30.25±5.25), (37.06±7.73) pg/ml] were significantly lower/higher than those of the model group [(261.02±10.88) ng/L, (23.64±2.09) pg/ml] (P<0.05, P<0.01 or P<0.001). At the same time, levels of TNF-α [(70.83±5.91), (57.83±8.20) ng/L] in the middle and high dose groups were significantly lower than those in the model group [(85.27±6.54) ng/L] (P<0.01 or P<0.001). Under the optical microscope, the degree of inflammation in the three dose groups of MgIG was less than that of the model group, and the degree of reduction increased with the dose.

Conclusion

MgIG can protect the liver damage caused by paclitaxel by changing the level of serum inflammatory factors and improving the degree of liver pathological tissue damage in rats.

表1 各组大鼠血清肝功能指标检测结果比较(U/L,
xˉ
±s
表2 MgIG对大鼠血清中IL-6、IL-10和TNF-α含量变化的影响(
xˉ
±s
图1 各组大鼠肝脏病理学改变(HE染色,×400)a为空白组,b 为模型组,c为低剂量组,d 为中剂量组,e为高剂量组
1
Morales-Cano D, Calviño E, Rubio V, et al. Apoptosis induced by paclitaxel via Bcl-2, Bax and caspases 3 and 9 activation in NB4 human leukaemia cells is not modulated by ERK inhibition [J]. Exp Toxicol Pathol, 2013, 65(7-8):1101-1108.
2
Ranjeeta B, Rajender RK. Drug-induced liver injury due to cancer chemotherapeutic agents [J]. Semin Liver Dis, 2014, 34(2):162-171.
3
Capel ID, Jenner M, Dorrell HM, et al. Hepatic function assessed (in rats) during chemotherapy with some anti-cancer drugs [J]. Clin Chem, 1979, 25(8):1381-1383.
4
Khan H, Nabavi SM, Sureda A, et al. Therapeutic potential of songorine, a diterpenoid alkaloid of the genus Aconitum[J]. Eur J Med Chem, 2018, 153:29-33.
5
Stage TB, Bergmann TK, Kroetz DL. Clinical pharmacokinetics of paclitaxel monotherapy: an updated literature review [J]. Clini Pharmacokinet, 2017, 57(1):7-19.
6
Jin Y, Hu W, Liu Tet al. Nogo-B receptor increases the resistance of estrogen receptor positive breast cancer to paclitaxel [J]. Cancer Lett, 2018, 419:233-244.
7
Li W, Chen Z, Shen S, et al. Protective effect of magnesium isoglycyrrhizinate combinated with verapamil on liver ischemia-reperfusion injury after semi-hepatectomy in rats [J]. Zhonghua Yi Xue Za Zhi, 2015, 95(38):3119-3123.
8
Wang W, Li X, Xu J. Magnesium isoglycyrrhizinate attenuates D-galactosamine/lipopolysaccharides induced acute liver injury of rat via regulation of the p38-MAPK and NF-κB signaling pathways [J]. Immunopharmacol Immunotoxicol, 2018, 40(3):262-267.
9
Zou X, Wang Y, Peng C, et al. Magnesium isoglycyrrhizinate has hepatoprotective effects in an oxaliplatin-induced model of liver injury [J]. Int J Mol Med, 2018, 42(4):2020-2030.
10
Wang Y, Wang Z, Gao M, et al. Efficacy and safety of magnesium isoglycyrrhizinate injection in patients with acute drug‐induced liver injury: A phase II trial [J]. Liver Int, 2019, 39(11):2102-2111.
11
Bocci G, Di Paolo A, Danesi R. The pharmacological bases of the antiangiogenic activity of paclitaxel [J]. Angiogenesis, 2013, 16(3):481-492.
12
Maha HS, Noha A, Nirmeen M, et al. Paclitaxel alleviates liver fibrosis induced by bile duct ligation in rats: Role of TGF-β1, IL-10 and c-Myc [J]. Life Sci, 2018, 211:245-251.
13
Yang Q, Zhang D, Li Y, et al. Paclitaxel alleviated liver injury of septic mice by alleviating inflammatory response via microRNA-27a/TAB3/NF-κB signaling pathway [J]. Biomed Pharmacother, 2018, 97:1424-1433.
14
Ali C, Ertan B, Belge KE, et al. N-acetylcysteine ameliorates methotrexate-induced oxidative liver damage in rats [J]. Med Sci Monit, 2006, 12(8):BR274-278.
15
Jing ZT, Liu W, Xue CR, et al. AKT activator SC79 protects hepatocytes from TNF-α-mediated apoptosis and alleviates d-Gal/LPS-induced liver injury [J]. Am J Physiol Gastrointest Liver Physiol, 2019, 316(3): G387-G396.
16
Malik G, Wilting J, Hess CF, et al. PECAM-1 modulates liver damage induced by synergistic effects of TNF-α and irradiation [J]. J Cell Mol Med, 2019, 23(5):3336-3344.
17
Afrin R, Arumugam S, Rahman A, et al. Curcumin ameliorates liver damage and progression of NASH in NASH-HCC mouse model possibly by modulating HMGB1-NF-κB translocation [J]. Int Immunopharmacol, 2017, 44:174-182.
18
Huang L, Zhao Z, Duan C, et al. Lactobacillus plantarum C88 protects against aflatoxin B(1)-induced liver injury in mice via inhibition of NF-κB-mediated inflammatory responses and excessive apoptosis [J]. BMC Microbiol, 2019, 19(1):170.
19
Sun Y, Gu J, Liu R, et al. IL-2/IL-6 ratio correlates with liver function and recovery in acute liver injury patients [J]. APMIS, 2019, 127(6):468-474.
20
Yousefi A, Zare Bidoki A, Shafioyoun A, et al. Association of IL-10 and TGF-beta cytokine gene polymorphisms with autoimmune hepatitis [J]. Clin Res Hepatol Gastroenterol, 2019, 43(1):45-50.
[1] 刘思锐, 赵辰阳, 张睿, 张一休, 杨萌. 多普勒超声对孕鼠子宫动脉不同节段血流动力学参数的评估[J/OL]. 中华医学超声杂志(电子版), 2024, 21(09): 877-883.
[2] 李朋, 苗立帅, 朱智奇. 四氢嘧啶对大鼠关节软骨细胞的保护作用[J/OL]. 中华关节外科杂志(电子版), 2024, 18(01): 69-77.
[3] 林琳, 田思萌, 于永华, 徐飞飞, 黄明莉. 干细胞及其外泌体治疗宫腔黏连的研究现状[J/OL]. 中华妇幼临床医学杂志(电子版), 2024, 20(03): 271-275.
[4] 杨文飞, 郝嘉文, 鲁梦远, 赵学刚, 李聪颖, 盖晨阳, 张晶, 张庆富. 高压电烧伤对大鼠心肌氧化应激的影响及N-乙酰半胱氨酸的干预作用[J/OL]. 中华损伤与修复杂志(电子版), 2024, 19(02): 106-112.
[5] 张礼刚, 邹志辉, 许顺, 蔡可可, 胡永涛, 梁朝朝. 酒精对慢性非细菌性前列腺炎中T淋巴细胞变化的影响研究[J/OL]. 中华腔镜泌尿外科杂志(电子版), 2024, 18(01): 74-81.
[6] 赛甫丁·艾比布拉, 买买提·依斯热依力, 李义亮, 王永康, 王志, 克力木·阿不都热依木. 不同材质补片修补对腹壁疝大鼠腹横筋膜组织转化生长因子-β1及Collagen合成代谢的作用[J/OL]. 中华疝和腹壁外科杂志(电子版), 2024, 18(02): 161-167.
[7] 张燕, 杨跃青, 邱峥. IgG 联合血清细胞因子对肺结核并发慢性肺曲霉菌病的诊断意义[J/OL]. 中华肺部疾病杂志(电子版), 2024, 17(05): 809-812.
[8] 刘锦程, 王斌, 张雯, 张明周, 刘禹, 叶东樊, 黄赞胜, 邱凌霄, 卿斌, 王创业, 王南博, 王苹, 郭宇航, 周培花, 程秋霞, 徐智. 肺泡灌洗液RASSF1A及SHOX2甲基化联合径向超声特征对肺结节性质鉴别诊断的意义[J/OL]. 中华肺部疾病杂志(电子版), 2024, 17(04): 505-511.
[9] 蒋丽芳, 林冰. 桑菊清解汤联合左氧氟沙星治疗社区获得性肺炎的临床分析[J/OL]. 中华肺部疾病杂志(电子版), 2024, 17(03): 458-461.
[10] 傅红兴, 王植楷, 谢贵林, 蔡娟娟, 杨威, 严盛. 间充质干细胞促进胰岛移植效果的研究进展[J/OL]. 中华细胞与干细胞杂志(电子版), 2024, 14(06): 351-360.
[11] 徐嘉愉, 张复华, 牛国敏, 梁家宝, 潘焕玉, 麦秀蕖, 杨国雷, 徐嘉良, 黄佑勇. Th1/Th2细胞因子谱在恶性血液肿瘤患者化疗后中性粒细胞缺乏伴感染的应用价值[J/OL]. 中华细胞与干细胞杂志(电子版), 2024, 14(03): 143-150.
[12] 阿卜杜萨拉木·图尔荪麦麦提, 吐尔洪江·吐逊, 温浩. 肝脏缺血-再灌注损伤与cGAS-STING信号通路[J/OL]. 中华肝脏外科手术学电子杂志, 2024, 13(03): 394-397.
[13] 杨智钧, 谷佳, 丁聿贤, 张正奎, 于如同. 脑胶质瘤患者血清炎性因子水平与病理分级及预后的相关性[J/OL]. 中华神经创伤外科电子杂志, 2024, 10(04): 238-242.
[14] 丛黎, 马林, 陈旭, 李文文, 张亮亮, 周华亭. 改良CT严重指数联合炎症指标在重症急性胰腺炎患者胰腺感染预测及预后评估中的研究[J/OL]. 中华消化病与影像杂志(电子版), 2024, 14(05): 432-436.
[15] 南朝涛, 陈建, 王书鸿, 李刚, 郝俊杰. 血清细胞因子预测急性脑梗死后肺炎的价值[J/OL]. 中华卫生应急电子杂志, 2024, 10(01): 16-20.
阅读次数
全文


摘要