| Cerebral ischemia is a kind of central nervous system disease featured with the reduction of brain blood flow. Cerebral ischemia is frequently observed in clinic and can significantly affect the quality of human life due to its comparatively high incidence rate, handicapped rate and death rate. According to the recent statistics from U.S., 85% patients among the 600,000 stroke patients every year are stroke due to cerebral ischemia, and the death rate is about20～50%. After cerebral ischemia, considerably number of blood vessels can be automatically revascularized or blood flow re-open after thrombolysis treatment. However, reperfusion injury comes with the revascularization. Many theories about cerebral ischemia and reperfusion injury have been proposed. These theories include free radical injury theory, excitatory amino acid toxicity theory, intracellular Ca2+ overload theory, acidosis theory, apoptosis theory and inflammatory immune reaction theory etc.In the recent years reseach results indicate that cytokines play an important role in the Cerebral ischemia damage, especially inflammatory cytokines such as IL-1β, IL-6 and TNF-α and so on involves in the progress of cerebral ischemia inflammation due to their powerful proinflammatory action. They can stimulate the production of other cytokines, adhesion molecules and inflammatory factors. They also can induce and promote leukocyte adherence to endothelial cell,and induce the migration of leukocyte from blood vessels to the ischemic brain tissues, which will accelerate the cerebral ischemia damage. Meanwhile, researchers also found that monocyte/macrophage, smooth muscle cells can secrete anti-inflammatory cytokines such as TGF(, IL-10, IL-4 and IL-13 etc. under certain conditions. Among which,IL-10 is a kind of anti-inflammatory cytokine with powerful immunoregulation and plays an important role in the immune response and inflammation response after cerebral ischemia. IL-10 can inhibit the monocyte-dependent Th1 cell growth, the formation and activity of many kinds of cytokines such as IL-1, TNF-α and IFN-γ etc. and can up-regulate the anti-inflammatory factor IL-lRa. In other countries, explorations have been made utilizing reconbinanent human IL-10 in the treatment of inflammatory diseases. Obviously,when the brain ischemia damage occurs,many kinds of pleiotropia cytokines will generate and form a cytokine network . However, the time course and effects of cytokines are different. When inflammatory cytokines play principle role, brain ischemia damage will be accelerated. Whereas anti-inflammatory cytokines do, they can protect the brain from ischemia damage. Thus, inhibiting the effect of inflammatory cytokines and increasing the effect of anti-inflammatory cytokines will eventually become an effective new pathway to the treatment and prevention of brain ischemia damage. It is a new possible pathway in the recent years in other countries that endogenous anti-inflammatory cytokines are induced for treating inflammatory diseases. Human monocyte/macrophage cell line U937 cells and brain ischemia/reperfusion injury rat model were used, techniques and methods such as cDNA arrays, ELISA, RT-PCR, Western blot and immunohistochemistry etc were appled. At cell research level, we studied the changes of IL-10 expression in U937 by LPS stimulation or hypoxia/reoxygenation process at cell and effects of drugs on the expression of IL-10. In vivo, we also studied the release of IL-10 in serum and effects of drugs during the rat brain ischemia and reperfusion injury. Meanwhile, we observed the expression of IL-10 in rat ischemic brain tissue and the expression of its receptor as well as the effects of drugs during the rat cerebral ischemia and reperfusion injury. Three drugs up-regulating the expression of endogenous anti-inflammation cytokines were discoved,the mechanism of which protecting brain ischemia-reperfusion injury were studied further at molecular research level . Theoretical basis for a new perspective in the exploring drugs for prevention and tre... |
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