右美托咪定预处理对2型糖尿病大鼠缺血再灌注脑损伤的作用

Influence of Dexmedetomidine on Cerebral Injury in Diabetic Rats

目的:探讨右美托咪定预处理对2型糖尿病大鼠缺血再灌注脑损伤的影响及机制。方法:雄性SD大鼠60只建立2型糖尿病大鼠模型,随机分为假手术组(S组)、缺血再灌注组(I/R组)、右美托咪定组(D组),建立全脑缺血再灌注损伤模型。缺血前30 min D组静脉输注右美托咪定0.05μg·kg-1·min-1,S组和I/R组静脉输注0.9%生理盐水2 m L/h,持续输注120 min。于缺血再灌注24 h对各组进行神经功能缺损评分(NDS评分),检测脑组织含水量,脑组织丙二醛(MDA)、超氧化物歧化酶(SOD)、过氧化氢酶(CAT),血浆白细胞介素6(IL-6)、肿瘤坏死因子α(TNF-α)水平,以及脑组织凋亡细胞水平。结果:S组、I/R组和D组NDS评分分别为4.25±3.15、45.56±8.59和23.00±8.83,D组显著高于S组(t=8.00,P<0.05)而低于I/R组(t=7.32,P<0.05);三组脑组织相对含水量分别为59.58±0.06、87.87±0.06和80.52±0.04,D组显著高于S组(t=116.21,P<0.05)而低于I/R组(t=40.76,P<0.05);三组MDA分别为0.89±0.13,2.67±0.52和1.85±0.51(nmol/mg),D组显著高于S组(t=7.29,P<0.05)而低于I/R组(t=4.50,P<0.05);SOD分别为82.33±13.17、32.06±6.34和57.89±9.74(U/mg),D组显著低于S组(t=5.97,P<0.05)而高于I/R组(t=8.89,P<0.05);CAT分别为85.13±9.08、22.25±3.69和52.43±6.75 CAT(U/mg),D组显著低于S组(t=5.96,P<0.05)而高于I/R组(t=8.89,P<0.05);三组大鼠血清IL-6分别为51.06±6.24、117.77±6.93和92.14±4.34(pg/mL),D组显著高于S组(t=21.62,P<0.05)而低于I/R组(t=12.54,P<0.05),TNF-α分别为40.98±9.29、85.31±9.64和55.89±7.39(pg/mL),D组显著高于S组(t=5.02,P<0.05)而低于I/R组(t=9.69,P<0.05);三组大鼠细胞凋亡分别为30.25±4.65,91.25±3.37和62.25±7.40,D组显著高于S组(t=14.65,P<0.05)而低于I/R组(t=14.27,P<0.05)。结论:右美托咪定预处理通过抑制炎症和氧化应激反应,降低神经细胞凋亡,对2型糖尿病大鼠全脑缺血再灌注损伤产生了保护作用。

Objective To observe the effect of dexmedetomidine on cerebral injury in type 2 diabetic rats. Methods Sixty male, Sprague-Dawley rats （200-220 g） as animal models with type 2 diabetes mellitus were established . The rat models were randomly divided into 3 groups： sham-operation group（group S） , ischemic-reperfusion control group （group I/R） and dexmedetomidine group（group D）, with 16 rats in each group. The animal models with global cerebral ischemia were established. The rats in group D, on 30 rain before ischemia,were in- fused with dexmedetomidine 0.05 μg·kg-1 ·min -1 over 120 min, while the rats in group S and group I/R were given 0.9% sodium chloride solution 2ml/h instead. Neurologic deficit scores, brain water content, SOD activity, CAT activity, and MDA content of brain tissue and the IL-6, TNF-α in the plasma were tested, the number of TUNEL-positive neurons in ischemic hippocampus were observed 24 h after reperfusion. Results The NDS scores were 4.25±3.15,45.56±8.59 and 23.00±8.83 for group S, group I/R and group D respectively, which indicated D group was significantly higher than S group（t=8.00, P 〈 0.05） but statistically lower than I/R group（t= 7.32, P 〈 0.05）;The brain water contents were 59.58±0.06, 87.87±0.06 and 80.52±0.04 for S group, I/R group and D group respectively, which indicated D group was significantly higher than S group（t=ll6.21, P 〈 0.05） but statistically lower than I/R group（t=40.76, P 〈 0.05）. The MDA were 0.89±0.13,2.67±0.52 and 1.85±0.51 （nmol/mg） for S group, I/R group and D group respectively, which indicated D group was significantly higher than S group（t=7.29, P 〈 0.05） but statistically lower than I/R group（t=4.50, P 〈 0.05）. The SOD were 82.33±13.17, 32.06±6.34 and 7.89±9.74（U/mg） for Sgroup, I/R group and D group respectively, which indicated D group was significantly lower than S group（t=5.97, P 〈 0.05） but statistically higher than I/R group（t=8.89, P 〈 0.05）. The CAT were 85.13±9.08,22.25±3.69 and 52.43±6.75 CAT（U/mg） for S group, I/R group and D group respectively, which indicated D group was significantly lower than S group（t=21.62, P 〈 0.05） but statistically higher than I/R group（t=8.89, P 〈 0.05）. The serum IL-6 were 51.06±6.24,117.77±6.93 and 92.14±4.34（pg/mL） for S group, I/R group and D group respectively, which indicated D group was significantly higher than S group（t=21.62, P 〈 0.05） but statistically lower than I/R group（t=12.54, P 〈 0.05）. The serum levels of TNF-α were 40.98±9.29, 85.31±9.64 and 55.89±7.39（pg/mL） for S group, I/R group and D group respectively, which indieated D group was significantly lower than S group（t= 5.02, P 〈 0.05） but statistically higher than I/R group（t=9.69, P 〈 0.05）. The apoptosis were 30.25±4.65,91.25± 3.37 and 62.25±7.40 for S group, I/R group and D group respectively, whieh indieated D group was significantly lower than S group（t=14.65, P 〈 0.05） but staitistieally higher than I/R group （t=14.27, P 〈 0.05）. Conclusion The dexmedetomidine has protective effeets on global cerebral ischemia-repeffusion injury in diabetic rats.