Knockdown Of Tissue Inhibitor Of Metalloproteinase 1 Suppresses Cell Apoptosis In Cerebral Infarction Rat Model

Cerebral infarction is a kind of ischemic stroke that severely threatens patient's health and life. Tissue inhibitor of metalloproteinase 1 (TIMP1) is reported to be promoted in the brain of middle cerebral artery occlusion (MCAo)-induced rabbit model, but its roles in regulating cerebral infarction are not fully understood. This study aimed at revealing the expression and function of TIMP1 in cerebral infarction. MCAo-induced cerebral infarction rat model was used to analyze TIMP1 expression in the brain. TIMP1-specific small interfering RNA was intracerebroventricularly injected before model construction. Brain histological observation was performed to analyze infarction area by TTC staining and cell apoptosis by TUNEL assay. Results showed that both mRNA and protein levels of TIMP1 were up-regulated in brain of cerebral infarction rat model compared to sham operation group (P < 0.001). Knockdown of TIMP1 reduced infarction area (P < 0.05) and suppressed cell apoptosis in brain cortex and hippocampus (P < 0.01), which was also confirmed by the expression changes of cell apoptosis indicators B-cell lymphoma extra-large (Bcl-XL) and caspase 3 (CASP3). These results suggest that knockdown of TIMP1 can suppress cerebral infarction progression and cerebral cell apoptosis in rat model, implying the pro-apoptotic roles of TIMP1 in cerebral infarction. So TIMP1 is a potential target for treating cerebral infarction, but further mechanism research is still necessary.