米诺环素对慢性低氧高二氧化碳模型小鼠小胶质细胞活化的影响

目的：观察米诺环素对慢性低氧高二氧化碳模型的小鼠小胶质细胞活化的影响。方法：C57BL/6野生小鼠30只随机分为3组：空白对照组（NC组）、盐水造模组（MS组）、米诺环素造模组（MM组）。将造模组小鼠置于常压低氧高二氧化碳舱内,通过氮气调节舱内氧浓度,使其维持在9%～11%,通入二氧化碳使其浓度维持在5%～6%,每天8 h,共4周。造模2周后,每天造模结束MM组立即腹腔注射米诺环素（45 mg/kg）,MS组以等量的0.9%氯化钠溶液腹腔注射。小鼠饲养到规定时间后,用10%水合氯醛腹腔注射麻醉,处死小鼠快速分离出两侧海马,右侧用于免疫组化检测小胶质细胞的活化,左侧用于荧光定量PCR测定IBA-1 mRNA、MMP-9 mRNA的表达。结果：NC组海马区可见静息态、呈树枝状、胞体小、突起多的小胶质细胞,MS组可见胞体肥大、突起较少的小胶质细胞,MM组有散在的小胶质细胞激活。与NC组相比,MS组IBA-1 mRNA、MMP-9 mRNA表达上调;与MS组相比,MM组IBA-1 mRNA、MMP-9 mRNA表达减少。结论：慢性低氧高二氧化碳环境下小鼠海马区IBA-1表达上调,提示有一定程度的小胶质细胞激活;米诺环素可抑制慢性低氧高二氧化碳对小鼠小胶质细胞活化,这可能与减少MMP-9的分泌有关。

Minocycline inhibits the mice's microglia activation caused by chronic hypoxia-hypercapnia

Objective: To observe the effects of minocycline on mice’s microglia activation induced by chronic hypoxia-hypercapnia.Methods: Thirty C57BL/6 mice were divided randomly into three groups:the control group(NC),the chronic hypoxia-hypercapnia-saline group(MS)and the chronic hypoxia-hypercapnia-minocycline group(MM).The latter two groups were placed in the special closed cabin with hypoxia and hypercapnia for 8 hr a day,4 weeks,in which there was O2 9%～11% and CO2 5%～6%.After 2 weeks the MS group was injected intraperitoneally with saline while the MM group was treated with 45 mg/kg minocycline respectively.when fed to the required time,all the mice were anesthetized with 10% chloral hydrate intraperitoneally,and then sacrificed.The hippocampus was quickly isolated,the right hippocampus was used for detection of the microglia activation by immunohistochemisty,and the left side was used for determination the expression of IBA-1 mRNA,MMP-9 mRNA by real time PCR.Results: The hippocampus of the NC group had brown scattered microglia(resting state,dendritic,small cell body,more processes),the MS group had some degrees of microglia activation(hypertrophy cell body,less neurite),and the MM group had scattered microglia activation.Compared with that of the NC group,expression of IBA-1 mRNA and more MMP-9 mRNA was more increased in the MS group.however,in the MM group expression of IBA-1 mRNA and MMP-9 mRNA was less increased compared with that of the MS group.Conclusion: Some degrees of microglia activation in the mice’s hippocampus may be induced by chronic hypoxia-hypercapnia;Minocycline may inhibit the mice’s microglia activation induced by chronic hypoxia-hypercapnia,and its mechanism may be associated with decreasing the MMP-9 secretion.