肌苷对新生大鼠缺氧缺血性脑损伤细胞色素C基因表达的影响

Effects of Inosine on Expression of Cytochrome C mRNA in Hypoxic-ischemic Brain Damage in Neonatal Rat Models

目的观察肌苷对新生大鼠缺氧缺血性脑损伤(HIBD)细胞色素C(CytC)基因表达的影响。方法新生7日龄SD大鼠75只随机分为正常对照组、肌苷治疗组和HIBD组(各组n=25)。分别于HI后6h、12h、1d、3d、7d制备标本,肌苷组于HI后即刻起给予肌苷100mg/kg,腹腔注射,每日2次,连续7d,采用原位杂交技术测定CytCmRNA表达情况。结果正常对照组可见少许CytC阳性细胞;HIBD组在HI后6hCytC阳性细胞增多,于HI后1d达峰值,与正常对照组相比差异具有显著性(P<0.05),之后逐渐下降,HI后7d仍明显高于正常组(P<0.05)。肌苷治疗组神经细胞CytCmRNA表达变化规律与HIBD组基本一致,各时间点与HIBD组相应时间点比较,阳性细胞数明显减少,差异有显著性(P<0.05)。结论HI损伤后给予肌苷干预能使脑皮质区及CA1区CytCmRNA表达下调,提示肌苷可能通过抑制CytCmRNA表达从而起到减少细胞凋亡保护神经元的作用。

Objective To study the effect of inosine on neuronal apoptosis and cytochrome C mRNA expression in the hypoxic- ischemic brain damage （HIBD） in neonatal rat models. Methods Seventy - five sprague - Dawley rat pups （aged 7 days） were randomly divided into normal control, inosine treatment group （100mg/kg inosine intraperitoneally administrated twice a day for 7 consecutive days） and HIBD group （each n = 25）. Animals were sacrificed at 6h, 12h, 1d, 3d, and 7d after HI. Hybridization in situ method was used to study t CytC mRNA expression. Results In the normal control, there were a few CytC positive cells. In the HIBD group, at 6h after HI, the number of CytC positive cells started to increase, peaked at ld, and decreased thereafter, but still higher during the 7th day after HI. In the inosine group, at every time point, the number of CytC positive cells was significantly less than that in the HBID group（P〈 0.0.5）. Conclusions Inosine can downregulate the expression of CytC mRNA induced by HI. The possible mechanism of the neuroprotection of inosine may re- late to the ＂downregulation of CytC mRNA expression - decrease of apoptosis＂ pathway.