氯沙坦对自发性高血压大鼠肾脏组织Bax、Bcl-2表达的影响情况

The effect of losartan on the expression of Bax and Bcl-2 in renal tissue of SHR rats

目的探讨氯沙坦对自发性高血压(SHR)大鼠肾脏组织Bcl-2相关性蛋白X(Bax)和B细胞淋巴瘤-2(Bcl-2)表达的影响。方法选取近交系雄性SHR大鼠30只和Wistar-Kyoto雄性大鼠15只,SHR大鼠随机分为氯沙坦组(n=15)和SHR阳性对照组(n=15),氯沙坦组按氯沙坦30 mg/kg灌胃,SHR阳性对照组按0.9%氯化钠溶液10 ml/kg灌胃,Wistar-Kyoto大鼠作为正常对照组,按0.9%氯化钠溶液10ml/kg灌胃,每日清晨灌胃,连续灌胃8周。比较各组大鼠尾动脉收缩压,采用免疫组化染色法检测两组Bax和Bcl-2蛋白表达,采用荧光定量聚合酶链反应(PCR)检测Bax和Bcl-2 m RNA表达水平。结果氯沙坦组给药第4周和8周尾动脉收缩压明显低于给药前收缩压水平(P<0.05);氯沙坦组给药第4周和8周尾动脉收缩压低于SHR阳性对照组(P<0.05);氯沙坦组和正常对照组Bcl-2平均光密度分别为(0.19±0.01)和(0.20±0.02),明显高于SHR阳性对照组(P<0.05),而Bax平均光密度分别为(0.12±0.02)和(0.13±0.01),明显低于SHR阳性对照组(P<0.05);氯沙坦组和正常对照组Bax和Bcl-2平均光密度比较差异无统计学意义(P>0.05);Bcl-2和Bax m RNA相对表达量在氯沙坦组和正常对照组间差异比较无统计学意义(P>0.05),SHR阳性对照组患者的Bcl-2相对表达值显著高于氯沙坦组和正常对照组,而Bax m RNA相对表达值显著低于氯沙坦组和正常对照组(P<0.05)。结论氯沙坦对SHR大鼠有明显的降压作用,可抑制Bax基因及蛋白表达,而促进Bcl-2基因及蛋白表达。

Objective To investigate the effect of losartan on expression of Bax and Bcl-2 in renal tissue of spontaneously hypertensive (SHR)rats. Methods 30 male SHR rats and 15 male Wistar-Kyoto rats were selected.SHR rats were randomly divided into two groups: losartan group (n=15) and SHR positive control group (n=15),losartan group was administered losartan 30 mg/kg by gavage; SHR positive control group was administered 10mL/kg of 0.9% sodium chloride solution by gavage; as normal control group, Wistar-Kyoto rats were administered 10mL/kg of 0.9% sodium chloride solution by gavage. All the rats were intragastrically administered every morning for 8 weeks. We compared systolic blood pressure of each group, expression of Bax and Bcl-2 in two groups were detected by immunohistochemical staining. The level of Bax mRNA and Bcl-2 mRNA were detected by fluorescence quantitative polymerase chain reaction (PCR). Results Tail artery systolic pressure of losartan group after administered 4 weeks and 8 weeks was significantly lower than before administration (P<0.05). Tail artery systolic pressure of losartan group after administered 4 weeks and 8 weeks was significantly lower than SHR positive control group (P<0.05). The average optical density of Bcl-2 in losartan group and normal control group were (0.19±0.01) and (0.20±0.02) respectively, which were significantly higher than SHR positive control group (P<0.05).The average optical density of Bax in losartan group and normal control group were(0.12±0.02) and (0.13±0.01) respectively, which were significantly lower than SHR positive control group (P<0.05). There was no significant difference in average optical density of Bax and Bcl-2 between the losartan group and the normal control group (P>0.05). As to relative expression of Bcl-2 mRNA and Bax mRNA, there was no significant difference between losartan group and the normal control group(P>0.05). The relative expression of Bcl-2 mRNA in SHR positive control group was significantly higher than losartan group and the normal control group; but the relative expression of Bax mRNA in SHR positive control group was significantly lower than Losartan group and the normal control group (P<0.05). Conclusion Losartan has a significant effect on the reduction of blood pressure in SHR rats, which can inhibit the expression of mRNA and protein of Bax, and promote the expression of mRNA and protein of Bcl-2.