| Abstract : Objective : To investigate the effects of ischemic postconditioning on the expression of Interleukin-6 (IL-6) and supressor of cytokine signaling-3 (SOCS-3) in the focal cerebral ischemia/reperfusion (CI/RP ) in rats. And to discuss the protective effect and its possible mechanism of ischemic postconditioning to cerebral ischemia/reperfusion injury.Methods: One hundred and forty male SD rats were randomly divided into three groups: sham-operation group (sham) (n=40), ischemia/reperfusion group (I/R) (n=50), ischemic postconditioning group (IPO) (n=50). Each group was observed at seven time point, which were 3h, 6h, 12h, 24h, 48h, 72h and 7d after the operation. And at each time point five rats were observed. In sham group, five rats were taken to do TTC staining at 24h after the operation. And in the I/R group and the IPO group, every five rats at the each time point of 24h, 72h and 7d after ischemia 90min were done TTC staining to measure the volume of cerebral infarction. The rat focal cerebral ischemia / reperfusion model adopted the modified suture method. In the IPO group, before the reperfusion, the rats had 15s reperfusion and then 15s ischemia, and repeated three times, while the sham group didn't have the suture. The grade of the neurologic deficits was measured at each time point after the operation. Water content of brain tisue was detected by the dry-wet weight method at different time point. Use Enzyme linked immunosorbent assay( ELISA)method to detect the IL-6 content in the brain tissue at different time point. TTC staining was used to measure the cerebral infarction volume. Histopathological changes of the cerebral infarction tissue detected by HE staining. Use Real-time PCR to detect the expression of SOCS-3mRNA in the brain tissue at different time point. Results: 1. changes of the neurologic deficits score:Neurologic deficits score of the I/R group at each corresponding time point which in 3h～7d after the operation was obviously lower than the sham group (P<0.05); at each time point of the I/R group, the neurologic deficits score at 24h was the lowest, which was greatly different from other time point (P<0.05). Neurologic deficits score of the IPO group at each corresponding time point which in 3h～7d was obviously lower than the sham group (P<0.05); and neurologic deficits score at each corresponding time point which in 12h～7d was obviously higher than the I/R group (P<0.05). 2. Changes of water content in brain tissue: Water content of the brain tissue in the I/R group was obviously higher than the sham group at each corresponding time point which in 6h～7d after the operation(P<0.05); at each time point of the I/R group the water content of the brain tissue elevated at 6h and reached the peak at 24h, which was greatly different from other time point (P<0.05). And then the water content descended, and cannot back to its normal level at 7d (P<0.05). Water content of brain tissue of the IPO group was obviously higher than the sham group at each corresponding time point which in 6h～72h (P<0.05); and water content of brain tissue was obviously lower than the I/R group at each corresponding time point which in 6h～7d(P<0.05). 3. IL-6 content in brain tissue: The IL-6 content in brain tissue of the I/R group was obviously higher than the sham group at each corresponding time point which in 3h～7d after the operation ( P<0.05); at each time point of the I/R group, the IL-6 content in the brain tissue elevated at 3h and reached the peak at 24h, which was greatly different from other time point (P<0.05). And then the IL-6 content descended, and cannot back to its normal level at 7d (P<0.05). The IL-6 content in brain tissue of the IPO group was obviously higher than the sham group at each corresponding time point which in 6h～72h (P<0.05); and the IL-6 content in brain tissue was obviously lower than the I/R group at each corresponding time point which in 6h～48h (P<0.05). 4. detection of the volume of the cerebral infarction: no focal cerebral infarction appeared in the sham group; the volume of cerebral infarction in the I/R group was the biggest at 72h after the operation, which was greatly different from those at 24h and 7d (P<0.05); the volume of the cerebral infarction of the IPO group was obviously smaller than those of the I/R group at each corresponding point which in 24h, 72h and 7d after the operation (P<0.05). 5. pathological changes of the brain tissue: no pathological injury appeared in the sham group. The I/R group presented the typical ischemic change, such as the thinner of the dyeing of the ischemic zone, the obvious reduction of the neurons and spongiocyte, the degeneration of the physaliphore, cell nucleus pyknosis shaping a triangle, the disappearance of the nucleolus,inflammatory cell infiltration, cell swelling,glial cell hyperplasia.Compared with the I/R group, the IPO group had a lower degree of the nerve cells necrosis, cellular edema, inflammatory cell infiltration. 6.The changes of SOCS-3mRNA expression in brain tissue:The SOCS-3mRNA expression of the I/R group was obviously higher than that of the sham group at each corresponding time point which in 3h～72h after the operation (P<0.05); in the I/R group, the expression of SOCS-3mRNA reached its highest at 24h after the operation (P<0.05), which was greatly different from other time point. And then it gradually decreased, and had no statistical significance at 7d. The SOCS-3mRNA expression of the IPO group was obviously higher than that of the sham group at each corresponding time point which in 3h～72h after the operation(P<0.05); and the SOCS-3mRNA was obviously higher than that of the I/R group at each corresponding time point in 12h～72h.Conclusion: 1. The improved model of focal cerebral ischemia/reperfusion (CI/RP ) in rats which was basically consistent with the human cerebral ischemia/reperfusion pathology physiology change, can be easily made and operated and with fine repeatability. It was a more ideal animal model to research the cerebral ischemia/reperfusion injury. 2. After the cerebral ischemia/reperfusion, the water content of brain tissue increased, the pathology of cerebral organization changed, the neurological function damaged and the expression of IL-6, SOCS-3 elevated. SOCS-3 possibly can suppress the expression of IL-6, hereby can reduce the reperfusion injury and had the endogenous neuroprotective effects. 3.Ischemic postconditioning can improve the neurological function, reduce brain edema and the pathological damage and the cerebral infarction volume , which was injuryed after ischemia/reperfusion, thus it had protective effects on brain damage. 4.Through the surpression of the production of IL-6 , the elevation of the expression of SOCS-3 and the reduction of the inflammatory cell infiltration and so on, ischemic postconditioning can play an important role in neuroprotection. |
PDF Full Text Request