丹参素对新生大鼠缺氧缺血性脑损伤组织iNOS、NOS、NO的影响

Effect of Danshensu on the iNOS、NOS and NO level in neonatal rats with hypoxic-ischemic brain injury

目的:观察丹参素对新生大鼠缺氧缺血性脑损伤组织iNOS、NOS、NO的影响并探讨其脑保护作用机制。方法:将78只SD新生大鼠随机分成假手术组(n=6),缺氧缺血模型组(n=18),丹参素低剂量组(n=18),丹参素中剂量组(n=18),丹参素高剂量组(n=18)。通过结扎左颈总动脉和吸入8%低氧混合气制备缺氧缺血性脑损伤(HIBD)动物模型。假手术组不进行缺氧缺血处理。丹参素各治疗组按低、中、高剂量分别于造模后0、24h两个时点按15,30,60mg·kg-1腹腔注射用生理盐水稀释至0.5mL的丹参素注射液。缺氧缺血模型组及假手术组于相应时点腹腔注射生理盐水0.5mL。假手术组于缺氧缺血后6h,缺氧缺血模型组与各丹参素治疗组于缺氧缺血后6,24,48h断头取脑,测定脑组织匀浆iNOS、NOS、NO浓度。结果:与假手术组比较,缺氧缺血模型组新生大鼠大脑中iNOS在缺氧缺血后6h时变化不大;而在缺氧缺血24h后升高,应用丹参素治疗后回降,呈一定的量效关系,差异有统计学意义(P<0.05);NOS及NO在缺氧缺血后6,24,48h均升高,应用丹参素治疗后回降,且呈一定的量效关系,差异有统计学意义(P<0.05)。结论:丹参素能抑制nNOS、iNOS的产生,从而减少过高的NO的产生,而发挥对新生鼠HIBD时脑的保护作用。

OBJECTIVE To study the effect of Danshensu（DSS） on the iNOS.NOS and NO level in neonatal rats with hypoxic ischemic brain damage（HIBD） and investigate the neuroprotectivity effect of Danshensu against HIBD in neonatal rats. METHODS seventy eight seven-day-old Sprague-Dawley（SD） rat pups were sham-operated and treated with vehicle（normal saline injection） （Sham ＋ Veh） or hypoxia-ischemia（HI） and treated with either vehicle（HIBD＋ Veh）, or DSS 15 mg·kg^-1 ·d^-1 （HIBD＋DSS 15mg·kg^-1·d^-1）, DSS30 mg·kg^-1·d^-1（HIBD＋DSS30 mg·kg^-1·d^-1）, DSS60 mg·kg^-1·d^-1（HIBD＋DSS 6（1 mg·kg^-1·d^-1） by intraperitoneal injection 0 h, 24 h after HI. HIBD rat models were established by ligating the left common carotid artery,followed by exposure to 8% oxygen and 92% nitrogen for 2 hrs in the HIBD ＋ Veh and the HIBD ＋ DSS. The Sham＋ Veh was not subjected to HI. 78 rats were sacrificed 6 h,24 h,48 h after HIBD and the level of iNOS. NOS and NO in the brain were assessed. IlFNULTS The level of iNOS was not significantly increased in HIBD ＋ Veh than Sham ＋ Veh after 6 hours of HI（P〉0. 05） but was significantly increased after 24 hours of HI （P〈0. 05）. NOS and NO level was significantly increased in HIBD ＋ Veh than Sham ＋ Veh after 6 hours of HI（P〈0.05）. Compared to HIBD ＋ Veh, the level of NOS in HIBD ＋ DSS significantly reduced after 6 hours of HI in dose^dependent manner （P〈0. 05）, and iNOS level were significantly reduced after 24 hours of HI too. CONCLUSION Danshensu can prevent brain against HIBD by demoting the level of nNOS. iNOS and NO in the brain of neonatal rats with HIBD.