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

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

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