黄芩苷对D半乳糖诱导衰老大鼠拮抗脑老化糖基化氧化应激及胰岛素抵抗作用

目的 观察黄芩苷( baicalin,Bai)对D-半乳糖(D-gal)诱导大鼠体内蛋白非酶糖基化-氧化应激、醛糖还原酶(AR)活性、血糖、胰岛素抵抗(IR)及空间探索能力的作用.方法 除空白对照组外,其余大鼠均采用腹腔注射( ip) D-gal 150 mg·kg-1,qd×70d致病.D-gal处理大鼠28 d后,将大鼠按体重均衡随机分成5组,每组15只:模型对照组(二甲双胍150 ng·kg-1、氨基胍150 mg·kg-1)以及Bai高和低剂量组(300 ng·kg-1和150 mg·kg-1),然后继续ip D-gal处理,同时灌胃给予不同药物或蒸馏水(10ml·kg-1),qd×42 d；实验结束时,观察药物对D-半乳精诱导大鼠血糖(FBG)、果糖胺(FRA)、糖化血红蛋白(HbAlc)、晚期糖基化终末产物( AG Es)、胰岛素和丙二醛(MDA)含量,并计算胰岛素敏感指数(ISI),醛糖还原酶(AR)和超氧化物歧化酶( SOD)活性,以及测定Moris水迷宫空间探索能力的作用.结果 与空白对照组比较,D-gal处理大鼠出现FBG、FRA、HbAIc、AGEs和MDA及胰岛素含量增高,SOD活性和ISI降低,红细胞内AR活性增强(P＜0.01 );二甲双胍、氨基胍以及Bai高和低剂量,均能不同程度降低D-gal诱导大鼠FBG、FRA、HbAlc、AGEs和胰岛素含量(P＜ 0.01或0.05),提高ISI( P＜ 0.01),降低MDA含量而提高SOD活性,并明显抑制AR活性(P＜0.01或0.05),提高大鼠空间探索能力.结论 Bai能对抗D-gal致衰老大鼠IR,改善胰岛素敏感性,抑制糖基化-氧化应激反应、多元醇通路代谢以及炎症反应,改善大鼠空间探索能力.Bai的上述作用,呈量效关系.

The effects of baicalin on inhibiting brain aging, glycation-oxidative stress and insulin resistance in D-galactose-induced aging rats

Objective To observe the effects of baicalin （ Bai ） on non-enzymatic glycation （ NEG ） -oxida- tive stress, activity of aldose reductase, insulin resistance （ IR ） and spatial seeking ability in D-galactose （ D-gal ） - induced senile rats. Methods Except the blank control, a rat model induced by D-gal 150 mg.kg-1, intraperitoneal injection （ ip ）, qd×70 d] was established. 28 days after treatment with D-gal, the rat models were randomly divide into 5 groups （ 15 rats for each goup ）： model control, metfornfin （ Met, 150mg·kg^-1 ）, and pimagedine （ PG, 150mg·kg^-1 ）, Bai high dose group（ 300 mmg·kg^-1 ）and low dose group （ 150 mg·kg^-1 ）; then ip D-gal and different drugs or distilled water /p-treated qd for 42 days. In the end of the experiment, the contents of fasting blood glucose （ FBG ）, fructosamine （ FRA ）, glycosylated hemoglobin （ HbAlc ）, advanced glycation end-products （ AGEs ）, insulin, and malondialdehyde （ MDA ） were analyzed, the activity of aldose reductase （ AR ） and superoxide dismutase （ SOD ） were determined, insulin sensitivity index （ ISI ） was counted and spatial seeking ability by Morris water maze test was selected. Results As compared with blank control, the concentration of FBG, FRA, HbA 1 c, AGEs, insulin and MDA increased （ P〈 0.01 ）, SOD activity declined （ P 〈 0.01 ）, AR activity enhanced （ P 〈 0.01 ）, ISI reduced （ P 〈 0.01 ）, and spatial seeking ability significantly declined in the D-gal-induced rats ; as compared with the D-gal-induced aging rats, the contents of FBG, FRA, HbAlc, AGEs and insulin were reduced, AR activity was inhibited, SOD activity was elevated, and spatial seeking ability was significantly increased by using Met, PG, and Bai at high or low dose （ P 〈 0.05 or P 〈 0.01 ）. Conclusions Baicalin can antagonize insulin resistance, improve insulin sensitivity, inhibit formation of glycation products-oxidative stress and activity of rate-limiting enzyme AR in polyol pathway, suppress inflammatory reaction, and improve spatial seeking ability in D-gal-induced aging rats. The effects of baicalin reveals a dose-effect relationship.