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目的:观察大鼠脑出血后血肿周围组织48 h、72 h MMP-9、TIMP-1的表达,探讨新清开灵注射液干预大鼠脑出血血肿周围脑水肿的作用途径。方法:采用尾状核注射胶原酶的方法复制大鼠脑出血的动物模型,并给予新清开灵注射液进行干预。结果:脑出血组血肿周围脑组织各时间点MMP-9表达水平呈动态改变,模型组MMP-9水平48 h开始升高,72 h达高峰,皆有统计学意义(P<0.01)。与脑出血48 h模型组相比较,同一时间点新清开灵小剂量组、大剂量组血肿周围脑组织MMP-9表达均可显著降低(P<0.01)。与脑出血模型72 h组比较,同一时间点新清开灵小剂量组MMP-9表达减少,具有统计学意义(P<0.05),大剂量组MMP-9表达亦减少,在统计学上有显著差异(P<0.01)。脑出血组血肿周围脑组织TIMP-1各时间点表达水平均升高,在48 h达到高峰(P<0.01)。与脑出血48 h模型组相比较,同一时间点新清开灵大剂量组可使血肿周围脑组织TIMP-1表达降低(P<0.05)。72 h新清开灵各剂量组血肿可使TIMP-1表达减少,大剂量组TIMP-1表达减少更为明显(P<0.01)。结论:通过调节TIMP-1而干预MMP-9表达是新清开灵注射液减轻脑出血后急性期水肿的可能途径。
Objective: To observe the expression of MMP-9 and TIMP-1 at 48 hours and 72 hours after intracerebral hemorrhage in rats, and to explore the possible mechanism of Xin Qing Kai Ling Injection in treating cerebral edema around cerebral hematoma in rats. Methods: The model of intracerebral hemorrhage in rats was made by injection of collagenase into the nucleus caudatum, and the new Qingkailing injection was given for intervention. Results: The expression of MMP-9 in cerebral hemorrhage group was changed dynamically at different time points. The level of MMP-9 in cerebral hemorrhage group began to increase at 48 h and peaked at 72 h (all P <0.01). Compared with the model group at 48 hours after intracerebral hemorrhage, the expression of MMP-9 in the brain tissue around the hematoma in the high-dose group was significantly lower at the same time point (P <0.01). Compared with the 72 h group, the expression of MMP-9 in the low-dose Qingkailing low dose group was significantly decreased at the same time point (P <0.05), and the expression of MMP-9 in the high-dose group was also decreased Significant difference (P <0.01). The expression of TIMP-1 in brain tissue around hematoma increased at each time point and peaked at 48 h (P <0.01). Compared with the model group at 48 h after intracerebral hemorrhage, the expression of TIMP-1 in the brain tissue around the hematoma decreased significantly at the same time point (P <0.05). The hematoma of the new Qingkailing dose group at 72 h reduced the expression of TIMP-1, but decreased the expression of TIMP-1 in the high dose group (P <0.01). Conclusion: Intervention of MMP-9 expression through the regulation of TIMP-1 is a possible way for Xinqingkailing injection to reduce acute edema after intracerebral hemorrhage.