异甘草素对大鼠脑损伤后MMP-9和TIMP-1蛋白酶表达的影响

doi:10.3877/cma.j.issn.2095-9141.2021.04.002

目的

观察异甘草素（ISL）对创伤性颅脑损伤（TBI）大鼠脑组织基质金属蛋白酶-9（MMP-9）和金属蛋白酶组织抑制因子-1（TIMP-1）表达的影响。

方法

将30只体质量200~250 g、清洁级Wistar大鼠随机分为正常对照组（10只）、TBI模型组（10只）、ISL组（10只）。正常对照组予以正常喂养；TBI模型组和ISL组制备TBI模型，采用改良Feeney法建立自由落体撞击造成闭合性TBI；ISL组制模成功后2~4 h开始予ISL干预，用药剂量30 mg/（kg·d）灌胃，共用药2周。取材后采用ELISA法检测MMP-9和TIMP-1的表达。

结果

正常对照组大鼠脑组织中MMP-9表达较强，TBI模型组大鼠脑组织中MMP-9表达减弱，ISL组MMP-9表达较TBI模型组减弱，差异均有统计学意义（P<0.05）。正常对照组大鼠脑组织中TIMP-1表达明显，TBI模型组大鼠脑组织中TIMP-1表达减弱，ISL组大鼠脑组织中TIMP-1表达较TBI模型组增强，差异均有统计学意义（P<0.05）。

结论

ISL可使TBI大鼠微血管基底通透性降低，减轻脑水肿程度，其作用机制可能与增加TIMP-1表达以调节MMP-9平衡有关。

关键词: 颅脑损伤, 异甘草素, 基质金属蛋白酶-9, 金属蛋白酶组织抑制物-1

Objective

To observe the effect of isoliquiritigenin (ISL) on the expression of matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1) in brain tissue of rats with traumatic brain injury (TBI).

Methods

Thirty clean grade Wistar rats, weighing 200-250 g, were randomly divided into normal control group (n=10), TBI model group (n=10) and ISL group (n=10). The normal control group was given normal feeding; TBI model group and ISL group were established by modified Feeney method, and closed TBI was induced by free fall impact; The ISL group was given ISL intervention 2-4 h after successful modeling, and the dosage was 30 mg/(kg·d) by gavage for 2 weeks. The expressions of MMP-9 and TIMP-1 were detected by ELISA.

Results

The expression of MMP-9 was strong in normal control group and decreased in TBI model group, and the expression of MMP-9 in ISL group was weaker than in the TBI model group (P<0.05). The expression of TIMP-1 in the normal control group was evident and decreased in TBI model group, and the expression of TIMP-1 in ISL group was significantly higher than that in the TBI model group (P<0.05).

Conclusion

ISL can reduce the permeability of microvascular basement and reduce the degree of brain edema in rats with TBI, and its mechanism may be related to increasing the expression of TIMP-1 to regulate the balance of MMP-9.

Key words: Craniocerebral injury, Isoliquiritigenin, Matrix metalloproteinase-9, Tissue inhibitor of metalloproteinase-1

图1 大鼠脑组织病理图（×40）

表1 各组大鼠脑组织中MMP-9和TIMP-1表达（OD×10^-2）

组别	只数	MMP-9阳性表达	TIMP-1阳性表达
正常对照组	10	35.81±0.03	64.85±0.03
TBI模型组	10	33.81±0.02^a	21.53±0.03^a
ISL组	10	21.53±0.03^ab	42.78±0.05^ab
F值		7.310	7.050
P值		0.011	0.031

表1 各组大鼠脑组织中MMP-9和TIMP-1表达（OD×10^-2）

组别	只数	MMP-9阳性表达	TIMP-1阳性表达
正常对照组	10	35.81±0.03	64.85±0.03
TBI模型组	10	33.81±0.02^a	21.53±0.03^a
ISL组	10	21.53±0.03^ab	42.78±0.05^ab
F值		7.310	7.050
P值		0.011	0.031

[1]	Liu J, Xiong X, Sui Y. Isoliquiritigenin attenuates neuroinflammation in traumatic brain injury in young rats[J]. Neuroimmunomodulation, 2019, 26(2): 102-110.
[2]	Lee DG, Min JS, Lee HS, et al. Isoliquiritigenin attenuates glutamate-induced mitochondrial fission via calcineurin-mediated Drp1 dephosphorylation in HT22 hippocampal neuron cells[J]. Neurotoxicology, 2018, 68: 133-141.
[3]	Shi D, Yang J, Jiang Y, et al. The antioxidant activity and neuroprotective mechanism of isoliquiritigenin[J]. Free Radic Biol Med, 2020, 152: 207-215.
[4]	Alzahrani S, Ajwah SM, Alsharif SY, et al. Isoliquiritigenin downregulates miR-195 and attenuates oxidative stress and inflammation in STZ-induced retinal injury[J]. Naunyn Schmiedebergs Arch Pharmacol, 2020, 393(12): 2375-2385.
[5]	Alzahrani S, Zaitone SA, Said E, et al. Protective effect of isoliquiritigenin on experimental diabetic nephropathy in rats: Impact on Sirt-1/NFκB balance and NLRP3 expression[J]. Int Immunopharmacol, 2020, 87: 106813.
[6]	Alshangiti AM, Togher KL, Hegarty SV, et al. The dietary flavonoid isoliquiritigenin is a potent cytotoxin for human neuroblastoma cells[J]. Neuronal Signal, 2019, 3(1): NS20180201.
[7]	Cao LJ, Yan M, Ma YX, et al. Isoliquiritigenin protects against triptolide-induced hepatotoxicity in mice through Nrf2 activation[J]. Pharmazie, 2016, 71(7): 394-397.
[8]	Cao M, Zhan M, Wang Z, et al. Development of an orally bioavailable isoliquiritigenin self-nanoemulsifying drug delivery system to effectively treat ovalbumin-induced asthma[J]. Int J Nanomedicine, 2020, 15: 8945-8961.
[9]	Chen C, Huang S, Chen CL, et al. Isoliquiritigenin inhibits ovarian cancer metastasis by reversing epithelial-to-mesenchymal transition[J]. Molecules, 2019, 24(20): 3725.
[10]	Chen C, Shenoy AK, Padia R, et al. Suppression of lung cancer progression by isoliquiritigenin through its metabolite 2, 4, 2’, 4’-Tetrahydroxychalcone[J]. J Exp Clin Cancer Res, 2018, 37(1): 243.
[11]	郝文龙，荔志云. 异甘草素在脑胶质瘤治疗中的作用与进展[J]. 西北国防医学杂志, 2019, 40(4): 255-259.
[12]	Chi JH, Seo GS, Cheon JH, et al. Isoliquiritigenin inhibits TNF-α-induced release of high-mobility group box 1 through activation of HDAC in human intestinal epithelial HT-29 cells[J]. Eur J Pharmacol, 2017, 796: 101-109.
[13]	孙建军，周杰，李长栋, 等. 异甘草素对颅脑损伤大鼠IL-6和IL-10表达的影响[J]. 中华神经创伤外科电子杂志, 2021, 7(1): 12-16.
[14]	Gao Y, Lv X, Yang H, et al. Isoliquiritigenin exerts antioxidative and anti-inflammatory effects via activating the KEAP-1/Nrf2 pathway and inhibiting the NF-κB and NLRP3 pathways in carrageenan-induced pleurisy[J]. Food Funct, 2020, 11(3): 2522-2534.
[15]	Qi J, Cui J, Mi B, et al. Isoliquiritigenin inhibits atherosclerosis by blocking TRPC5 channel expression[J]. Cardiovasc Ther, 2020, 2020: 1926249.
[16]	李长栋，荔志云，白海, 等. 大黄素甲醚联合脐带间充质干细胞移植对创伤性脑损伤大鼠MMP-9和TIMP-1蛋白酶的影响[J]. 创伤外科杂志, 2013, 15(4): 306-309.
[17]	Ralay Ranaivo H, Hodge JN, Choi N, et al. Albumin induces upregulation of matrix metalloproteinase-9 in astrocytes via MAPK and reactive oxygen species-dependent pathways[J]. J Neuroinflammation, 2012, 9: 68.

[1]	任琼, 吴东燕, 李中花, 石晶, 张静, 耿丽伟. 血清降钙素原、基质金属蛋白酶-9和可溶性细胞间黏附分子-1联合检测对绒毛膜羊膜炎的诊断价值[J]. 中华实验和临床感染病杂志(电子版), 2023, 17(03): 194-199.
[2]	钱晓英, 吴新, 徐婷婷. 颅脑损伤并发呼吸衰竭患者早期机械通气的效果分析[J]. 中华肺部疾病杂志(电子版), 2023, 16(04): 526-528.
[3]	刘玲, 肖颖, 王蓉. 严重创伤并发肺部感染死亡病例分析[J]. 中华肺部疾病杂志(电子版), 2023, 16(04): 581-583.
[4]	李飞翔, 段虎斌, 李晋虎, 吴昊, 王永红, 范益民. 急性颅脑损伤继发下肢静脉血栓的相关危险因素分析及预测模型构建[J]. 中华神经创伤外科电子杂志, 2023, 09(05): 277-282.
[5]	潘立, 谢理政, 程宏伟, 茆翔. 创伤性颅脑损伤后垂体功能减退[J]. 中华神经创伤外科电子杂志, 2023, 09(05): 308-312.
[6]	王景景, 符锋, 李建伟, 任党利, 陈翀, 刘慧, 孙洪涛, 涂悦. 针刺对中型创伤性颅脑损伤后BDNF/TrkB信号通路的影响[J]. 中华神经创伤外科电子杂志, 2023, 09(04): 199-205.
[7]	张馨月, 韩帅, 张舒石, 李文臣, 张舒岩. 颅内压监测技术在创伤性颅脑损伤治疗中的应用[J]. 中华神经创伤外科电子杂志, 2023, 09(04): 246-252.
[8]	王守森, 黄银兴, 陈宇晖, 胡晓芳, 刘海兵. 重型颅脑损伤的外科救治策略[J]. 中华神经创伤外科电子杂志, 2023, 09(03): 190-192.
[9]	张永明. 颈段脊髓电刺激治疗颅脑损伤后慢性意识障碍的进展[J]. 中华神经创伤外科电子杂志, 2023, 09(03): 129-134.
[10]	王召, 田进杰, 郭朝, 王蕾, 严红燕, 冯素娟, 张毅. 血浆PGK1早期检测对创伤性颅脑损伤患者病情严重程度及预后的预测价值[J]. 中华神经创伤外科电子杂志, 2023, 09(03): 154-159.
[11]	何佳伟, 张良, 杨骐, 王占祥. 创伤性颅脑损伤后进展性出血性损伤的诊疗现状[J]. 中华神经创伤外科电子杂志, 2023, 09(03): 175-179.
[12]	贾素英, 李倩, 郭姗姗. 创伤性颅脑损伤后血小板功能障碍的研究进展[J]. 中华神经创伤外科电子杂志, 2023, 09(03): 180-185.
[13]	汤宏, 高灵, 高宁, 蒋俊文, 张吉坤, 李由, 陈伟明, 夏鹰. 控制性减压在治疗重型颅脑损伤中的应用[J]. 中华神经创伤外科电子杂志, 2023, 09(02): 91-96.
[14]	朱敏, 李法强. CD64指数联合降钙素原、白介素-6、血清淀粉样蛋白A检测对重型颅脑损伤术后颅内细菌感染的诊断价值[J]. 中华神经创伤外科电子杂志, 2023, 09(01): 26-31.
[15]	丁晶, 李培雯, 许迎春. 醒脑开窍针刺法在神经急重症中的应用[J]. 中华针灸电子杂志, 2023, 12(04): 161-164.

阅读次数

全文

摘要

选择文件类型/文献管理软件名称

选择包含的内容

Effects of isoliquiritigenin on the expression of MMP-9 and TIMP-1 protease after brain injury in rats

模态框（Modal）标题

选择文件类型/文献管理软件名称

选择包含的内容

Effects of isoliquiritigenin on the expression of MMP-9 and TIMP-1 protease after brain injury in rats