
浏览全部资源
扫码关注微信
400042 重庆,第三军医大学大坪医院野战外科研究所心血管内科,重庆市心血管病研究所
[曾春雨,E-mail:chunyuzeng01@163.com ZENG Chunyu, E-mail:chunyuzeng01@163.com
收稿:2017-08-20,
修回:2017-09-28,
纸质出版:2017-12-15
移动端阅览
周中淑, 巩正藩, 杨东海, 等. 重组人MG53对CCl4诱导的急性肝损伤的保护作用[J]. 第三军医大学学报, 2017,39(23):2270-2275.
Zhongshu ZHOU, Zhengfan GONG, Donghai YANG, et al. Protective effect of recombinant human mitsugumin 53 on CCl4-induced acute liver injury in mice[J]. Journal of Third Military Medical University, 2017, 39(23): 2270-2275.
周中淑, 巩正藩, 杨东海, 等. 重组人MG53对CCl4诱导的急性肝损伤的保护作用[J]. 第三军医大学学报, 2017,39(23):2270-2275. DOI: 10.16016/j.1000-5404.201708123.
Zhongshu ZHOU, Zhengfan GONG, Donghai YANG, et al. Protective effect of recombinant human mitsugumin 53 on CCl4-induced acute liver injury in mice[J]. Journal of Third Military Medical University, 2017, 39(23): 2270-2275. DOI: 10.16016/j.1000-5404.201708123.
目的
2
研究重组人MG53(rhMG53)对四氯化碳(CCl
4
)诱导的急性肝损伤的保护作用及其相关机制。
方法
2
40只雄性C57小鼠采用完全随机化分组法分成4组:正常对照组、rhMG53组、CCl
4
组、rhMG53+CCl
4
组,每组10只。CCl
4
组、rhMG53+CCl
4
组小鼠予0.1% CCl
4
花生油溶液2 mL/kg腹腔内注射,rhMG53+CCl
4
组在注射CCl
4
前30 min予rhMG53 1 mg/kg肌肉注射。rhMG53组予rhMG53 1 mg/kg肌肉注射。正常进食进水24 h后眼球取血分离血清,测定谷丙转氨酶(ALT)、谷草转氨酶(AST)、乳酸脱氢酶(LDH)活性。取小鼠肝脏
观察肝脏的组织学改变。以体外培养的人肝癌细胞(HepG2)为靶细胞,观察rhMG53对CCl
4
诱导的细胞损伤的保护作用。
结果
2
rhMG53降低小鼠血清ALT、AST、LDH水平,病理镜检显示rhMG53可改善肝脏的病理结构,差异均有统计学意义(
P
<
0.05);rhMG53可以修复HepG2细胞膜,保护CCl
4
对HepG2细胞的损伤。
结论
2
rhMG53改善CCl
4
诱导的急性肝细胞损伤,保护肝脏功能。
Objective
2
To determine the protective effect of recombinant human MG53 (rhMG53) on acute liver injury in mice induced by carbon tetrachloride (CCl
4
)
and investigate its underlying mechanism.
Methods
2
Male C57 mice (
n
=40) were randomly divided into 4 groups (
n
=10)
that is
normal control group
rhMG53 group
CCl
4
group
and rhMG53+CCl
4
group. The animals of the CCl
4
group and rhMG53+CCl
4
group were injected intraperitoneally with 0.1% CCl
4
peanut oil solution at a dose of 2 mL/kg
and the mice of the latter group were injected intramuscularly with 1 mg/kg rhMG53 in 0.5 h before
CCl
4
injection. In 24 h after normal feeding
blood samples were collected after eyeball extirpating
and the serum levels of alanine aminotransferase (ALT)
aspartate aminotransferase (AST) and lactate dehydrogenase (LDH) were measured. The liver tissues of the mice were also harvested for histological changes of the livers. Human hepatocellular carcinoma cells (HepG2) were used as target cells to observe the protective effect of rhMG53 on CCl
4
-induced cell injury.
Results
2
RhMG53 treatment reduced serum ALT
AST and LDH levels
and significant attenuated the pathological injuries induced by CCl
4
(
P
<
0.05). rhMG53 repaired cell membrane and reduced CCl
4
-induced damage to HepG2 cells.
Conclusions
2
rhMG53 shows protective effect on CCl
4
-induced acute hepatocellular injury and protects the liver function in mice.
KHOURY T, RMEILEH A A, YOSHA L, et al . Drug innduced liver injury: review with a focus on genetic factors, tissue diagnosis, and treatment options[J ] . J Clin Transl Hepatol, 2015, 3(2): 99-108. DOI:10.14218/JCTH.2015.00007.
OH I S, PARK S H. Immune-mediated liver injury in hepatitis B virus infection[J]. Immune Netw, 2015, 15(4): 191-198. DOI:10.4110/in.2015.15.4.191.
WEISLEDERN, TAKIZAWA N, LIN P, et al . Recombinant MG53 protein modulates therapeutic cell membrane repair in treatment of muscular dystrophy[J ] . Sci Transl Med, 2012, 4(139): 139ra85. DOI:10.1126/scitranslmed.3003921.
CAI C, MASUMIYA H, WEISLEDER N, et al . MG53 nucleates assembly of cell membrane repair machinery[J ] . Nat Cell Biol, 2009, 11(1): 56-64.DOI:10.1038/ncb1812.
ZHU H, HOU J, ROE J L, et al . Amelioration of ischemia-reperfusion-induced muscle injury by the recombinant human MG53 protein[J ] . Muscle Nerve, 2015, 52(5): 852-858. DOI:10.1002/mus.24619.
WANG X, XIE W, ZHANG Y, et al . Cardioprotection of ischemia/reperfusion injury by cholesterol-dependent MG53-mediated membrane repair[J ] . Circ Res, 2010, 107(1): 76-83. DOI:10.1161/CIRCRESAHA.109.215822.
CAO C M, ZHANG Y, WEISLEDER N, et al . MG53 constitutes a primary determinant of cardiac ischemic preconditioning[J ] . Circulation, 2010, 121(23): 2565-2574. DOI:10.1161/CIRCULATIONAHA.110.954628.
LIU J, ZHU H, ZHENG Y, et al . Cardioprotection of recombinant human MG53 protein in a porcine model of ischemia and reperfusion injury[J ] . J Mol Cell Cardiol, 2015, 80: 10-19. DOI:10.1016/j.yjmcc.2014.12.010.
JIA Y, CHEN K, LIN P, et al . Treatment of acute lung injury by targeting MG53-mediated cell membrane repair[J ] . Nat Commun, 2014, 5: 4387. DOI:10.1038/ncomms5387.
DUANN P, LI H, LIN P, et al . MG53-mediated cell membrane repair protects against acute kidney injury[J ] . Sci Transl Med, 2015, 7(279): 279ra36. DOI:10.1126/scitranslmed.3010755.
YAO Y G, ZHANG B, ZHU H, et al . MG53 permeates through blood-brain barrier to protect ischemic brain injury [J ] . Oncotarget, 2016, 7(16): 22474-22485.DOI:10.18632/oncotarget.7965.
CUBERO F J, ZOUBEK M E, HU W, et al . Combined activities of JNK1 and JNK2 in hepatocytes protect against toxic liver injury[J ] . Gastroenterology, 2016, 150(4): 968-981. DOI:10.1053/j.gastro.2015.12.019.
WEBER L W, BOLL M, STAMPFL A. Hepatotoxicity and mechanism of action of haloalkanes: carbon tetrachloride as a toxicological model[J]. Crit Rev Toxicol, 2003, 33(2): 105-136. DOI:10.1080/713611034.
ZHANG Y, WU H K, LV F, et al . MG53: biological function and potential as a therapeutic target[J ] . Mol Pharmacol, 2017, 92(3): 211-218. DOI:10.1124/mol.117.108241.
LI H, DUANN P, LIN P H, et al . Modulation of wound healing and scar formation by MG53 protein-mediated cell membrane repair[J ] . J Biol Chem, 2015, 290(40): 24592-24603. DOI:10.1074/jbc.M115.680074.
YAO W, LI H, HAN X, et al . MG53 anchored by dysferlin to cell membrane reduces hepatocyte apoptosis which induced by ischaemia/reperfusion injury in vivo and in vitro [J ] . J Cell Mol Med, 2017. [Epub ahead of print ] . DOI: 10.1111/jcmm. 13171..
0
浏览量
0
下载量
0
CSCD
关联资源
相关文章
相关作者
相关机构
京公网安备11010802024621