木犀草素对糖尿病脑梗死大鼠神经细胞凋亡及HSP70mRNA、FasmRNA表达的影响简

目的探讨木犀草素对糖尿病脑梗死大鼠神经细胞凋亡及HSP70mRNA、FasmRNA表达的影响。方法Wistar大鼠60例，随机分为对照组、模型组及木犀草素高、中、低剂量组。对照组给予常规饲料喂养；模型组及木犀草素高、中、低剂量组采用高脂高糖饮食加腹腔注射小剂量链脲霉素建立糖尿病大鼠模型，造模后，木犀草素高剂量、中剂量、低剂量组每日分别给予木犀草素200、100、50mg／kg灌胃，模型组每日给予生理盐水2mL灌胃，连续8周。再以线栓法建立大鼠大脑中动脉永久性缺血模型，术后24h断头取脑，用TUNEL法和原位杂交法观察大鼠脑细胞凋亡与脑组织HSP70mRNA及FasmRNA的表达。结果木犀草素低、中、高剂量组糖尿病脑梗死神经细胞凋亡数分别为（16．42±1．39）、（11．08±2．15）、（9．25±1．98）个／高倍视野低于模型组（29．75±2．36）个／高倍视野]，组间差异有统计学意义（均P〈0．01）；HSP70mRNA在模型组表达（9．75±2．766）个／高倍视野]显著高于对照组（0个／高倍视野）]（P〈0．01）；低、中、高三个剂量的木犀草素组HSP70mRNA表达分别为（11．33±2．15）、（13．92±2．15）、（14．92±1．95）个／高倍视野，均高于模型组（9．75±2．76）个／高倍视野]（均P〈0．01）；FasmRNA在模型组大鼠脑组织阳性细胞数（25．33±3．17）个／高倍视野]显著高于对照组（2．67±0．95）个／高倍视野]（P〈0．01）；高、中、低剂量木犀草素组大鼠脑组织FasmRNA阳性细胞数分别为（11．92±2．41）、（12．00±2．50）、（19．75±2．54）个／高倍视野，显著低于模型组（25．33±3．17）个／高倍视野]（均P〈0．01）。结论木犀草素可以抑制糖尿病脑梗死大鼠神经细胞凋亡，其机制与木犀草素升高大鼠脑组织HSP70mRNA表达，同时使FasmRNA的表达降低有关。

Effects of Luteolin on nerve cell apoptosis and expression of HSP70 mRNA and fas mRNA in diabetes Complicating with stroke rats

Objective To investigate the effect of Luteolin on nerve cell apoptosis and expression of HSPTO mRNA and Fas mRNA in diabetes complicating with stroke rats. Methods Sixty Wistar rats were randomly divided into normal control, diabetic model, low-dose Luteolin, mid-dose Luteolin and high-dose Luteolin group. Rats of control group were given conventional feed. Rat models of diabetes mellitus of diabetic model group and low-dose Luteolin, mid- dose Luteolin and high-dose Luteolin group were made by high sucrose, fat diet and streptozotion injection. After mod- eling, rats in high-dose Luteolin, mid-dose Luteolin and low-dose Luteolin group were administed daily with gastric perfusion of 200, 100 and 50 mg/kg Luteolin separately for 8 weeks, at the same time, model group was given saline daily 2 mL. Models of focal cerebral infarction of rats were established by the Longa＇s technique. All of the rats were killed after 24 hours, TUNEL and in situ hybridization were used to detect nerve cell apoptosis and expression of HSP70 mRNA and Fas mRNA in brain tissue of rats. Results The amount of nerve cell apoptosis in low, medium and high dose of Luteolin group of （16.42±1.39）, （11.08±2.15）, （9.25±1.98）/HD were lower than those of model group of （29.75±2.36）/HD, the difference was statistically significant （all P 〈 0.01）. Compared with control group of （O/HD）, the expression of HSP70 mRNA in model group of （9.75±2.76）/HD significant increased. The level of HSP70 mRNA ex- pression in low, medium and high dose of Luteolin group of （11.33_±2.15）, （13.92±2.15）, （14.92±1.95）/HD were signifi- cant higher than those of model group of （9.75±2.76）/HD （P 〈 0.01）. The amount of Fas mRNA positive cells in model group of （25.33±3.17）/HD was higher than that of control group of （2.67±0.95）/HD （P 〈 0.01）; in high, medium and low dose of Luteolin group, the amount of Fas mRNA positive cells of （11.92±2.41）, （12.00±2.50）, （19.75_±2.54）/HD were lower than those of model group of （25.33±3.17）/HD （P 〈 0.01）. Conclusion Luteolin can inhibit nerve cell apoptosis of diabetic cerebral infarction rats, its mechanism may be related to increasing the expression of HSP70 mRNA and decreasing the expression of Fas mRNA, thereby reducing the apoptosis of nerve cells.