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A Study Of The Regulatory Relationship Between MicroRNA-7 And PARP In Rat MCAO Model

Posted on:2017-02-23Degree:MasterType:Thesis
Country:ChinaCandidate:A R TanFull Text:PDF
GTID:2284330488497904Subject:Neurology
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Objectives:This study used a rat model of middle cerebral artery occlusion. To investigate the relationship between microRNA-7 and PARP in the rat MCAO model, and the effect of microRNA-7 on the cerebral ischemia injury and its molecular mechanism.Methods:The 60 healthy adult male rats were divided into 4 groups:shame group, pure cerebral infarction group, miR-7 agomir group, miR-7 antagomir group. The SD rat MCAO modle was induced with a suture to block blood flow. Using Longa Zea score to determine whether the model can enter the test. The miR-7 agomir or miR-7 antagomir was injected into SD rat ventricular to regulate the expression of miR-7 in rat brain. Using the mNSS score to evaluate neural function after the MCAO model was prepared 24 hours. With triphenyl tetrazolium chloride staining to identify infarction and non infarction of brain tissue. The expression of PARP was detected by immunohistochemisty. Detection of cell apoptosis in rat brain by TUNEL. Real-time PCR was used to detect the expression of miR-7. The expression of PARP was detected by Western blot.Results:1. The expression of miR-7 in the ischemic penumbra was decreased after MCAO: As compared with controls, the expression of miR-7 in the ischemic penumbra was significantly decreased after MCAO. This shows that miR-7 is involved in cerebral ischemia injury.2. The expression of miR-7 can be successfully regulated by the intra ventricular stereotactic injection of miR-7 agomir or miR-7 antagomir. Compared with the pure cerebral infarction group, the expression of miR-7 in miR-7 agomir goup was increased significantly, while the expression of miR-7 in miR-7 antagomir goup was significantly lower.3. MiR-7 inhibits the protein expression of PARP:Compared with the pure cerebral infarction group, agomir miR-7 group miR-7 expression increased, while PARP expression decreased; antagomir miR-7 group miR-7 expression was inhibited, while PARP expression increased. These results showe that miR-7 inhibites the expression of PARP, and PARP may be the target gene of miR-7.4. The effect of miR-7 expression on brain injury in MCAO:compared with the pure cerebral infarction group, treatment with miR-7 agomir decreased cerebral infarction size, and reduced cell apoptosis and neurological deficits. On the contrary, treatment with miR-7 antagomir increased the infarction size, and increased cell apoptosis neurological deficits. These results suggest that miR-7 plays an important role in the brain injury following cerebral ischemia, and overexpression of miR-7 can reduce the brain injury induced by cerebral ischemia.Conclusions:1. In rat MCAO model, the expression of miR-7 in the ischemic penumbra is decreased after cerebral ischemia 24 hours later.2. The expression of miR-7 can be successfully regulated by the intra ventricular stereotactic injection of miR-7 agomir or miR-7 antagomir.3. In rat brain, PARP may be the target gene of miR-7.4. Over expression of miR-7 can decrease cerebral infarction size, and reduce cell apoptosis and neurological deficits.5. In the rat MCAO model, miR-7 palys a protective role by inhibiting the expression of PARP.
Keywords/Search Tags:cerebral ischemia, miRNA, PARP, apoptosis
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