| For the high morbidity , mortality and disability rate, ischemic ceresro vascular diseases (ICVD) are seriously endangering people's health. The mechanisms of neuronal injury and death caused by ICVD have been deeply studied. Among many dangerous factors of ICVD, hypertension is most important and independent. Therefore cerebral ischemia models established with hypertensive animals approximate well to human's ICVD and improve the correlation between clinic and animal researches.In recent years, DNA damage and repair has been drawing more attention in the field of ischemic neuronal injury. It has been reported that overwhelming DNA damage against DNA repair could induce apoptosis in several different models. Some researches indicated that early reduction of DNA repair protein probably has correlation with subsequent DNA-damaged neuronal cell death after cerebral ischemic reperfusion. Because neuronal cell death is the basis of cerebral injury, researches about DNA damage and repair probably indicate the mechanism of neronal injury and death after ICVD, and bring new strategy for its therapy. Monosialoganglioside (GMi) has the function of attenuating neuronal apoptosis, but its mechanicm is not very clear.The purpose of this experiment is to explore the relation between the expression of DNA repair protein XRCCI and DNA fragmentation in neuronal cell after focal ischemia/reperfusion of renovascular hypertensive rats (RHR), and the mechanism by which GMi protect brain. Materials and Methods1. The 2-kidney, 2-clip method was used to induce hypertension in male healthy Sprague-Dawley rats with the ring-shaped sliver clips. Blood pressure were continuously observed from the second week after surgery to judge the success of RHR2. Middle cerebral artery occlussion (MCAO) by sulture emboli were established with RHR ( systolic blood pressure>160 mmHg) . Sham operated control rats received the operations without ischemia and lesion treatment. Horner's sign in left side and paralysis of the right front limbs were observed to judge the success of MCAO model.3. Groups of animals: Group I (n=24) Sham operated control group: normal blood pressure Sprague-Dawley rats; Group II (n=24) sham-operated control group: RHR; Group III (n=24) RHR+MCAO; Group IV (n=24) RHR+MCAO+GMi. In 12 hours, 5 minutes before surgery and 12 hours after surgery, GMi(20mg/Kg) was administered to rats via peritoneal injecton. The same dosage of nomal saline was administered to Group I, II and III at the same time. Anesthetized rats were perfused with 200 ml normal saline and subsequently with 4% polyformaldehyde in 0.1 mol phosphylate buffer follwed by 3h, 6h, 121u 24h after reperfusion in every group. Every subgroup includes 6 rats. Brains were removed, postfixed, embedded, sectioned and proccessed for TUNEL detection and XRCCI immunohistochemistry. The results of TUNEL were observed and evaluated under light microscope and those of immunohistochemistry were evaluated by image-quantative analysis system.All the datas were expressed by (x+s) and analyzed statistically by repeatedmeasure -, one way analysis of variance , t- test and linear correlation. The testingstandard was a=0.05. Results: 1 . The level of blood pressure began to increase since 2 weeks after surgery andmaintained to increase until 1 6 weeks after surgery, indicating the suceess of RHRmodel.2. Rats in Group III and IV showed Horner's sign in left side and paralysis of the right front limbs after focal cerebral ischemia, and rats in Group I and II only showed Horner's signs in left side, indicating the suceess of MCAO model.3. TUNEL detection: There was no postive cell at ischemic cortex and the CA1 region of hippocampus in Group I and II. There were plenty of postive cells at the same area in Group III . Compared with Group III, the number of ositive cells in Group D at ischemia Ih/reperfusion 24h was significantly lower respectively (P<0.05). These results indicated that GMi reduced significantly DNA fragmentation in the i...
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