黄连素对链脲佐菌素糖尿病大鼠GH/IGF-Ⅰ轴的影响

The influence of berberine on GH/IGF-Ⅰ axis in streptozotocin induced diabetic rats

目的通过链脲佐菌素(STZ)诱导糖尿病大鼠模型探讨黄连素(BBR)对糖尿病GH/IGF-Ⅰ轴的影响及其机制。方法选取Sprague-Dawley雄性大鼠48只,随机均分为正常对照组(NC)、糖尿病组(DC)、胰岛素治疗组(INS)和黄连素(BBR)治疗组四组,每组各12只。NC组不予特殊处理,DC组STZ诱导后不予特殊处理,INS组STZ诱导后予中效胰岛素皮下注射处理,BBR组STZ诱导后予BBR灌胃处理,上述四组实验持续8周;实验期间监测尾尖血糖和体重,采用酶免疫检测法检测血清中GH及IGF-Ⅰ,采用PCR技术检测垂体中GH及肝脏中IGF-Ⅰ、IGFBP-3、GHR基因的表达情况。结果 DC组血糖在实验期间始终维持在较高水平;INS组治疗后血糖与NC组相比差异无统计学意义;BBR组治疗后血糖水平位于NC组与DC组之间且与两组的差异均具有统计学意义;DC组垂体组织中GH基因(mRNA)的表达较NC组明显增强,INS组及BBR组治疗后有所下降;DC组肝脏中GHR表达量明显减少,INS组及BBR组治疗后有所上调;DC组肝脏中的IGF-Ⅰ的表达量明显减少,INS组及BBR组治疗后有所增强;DC组肝脏中IGFBP-3的表达量明显减少,INS组及BBR组治疗后有部分上调。结论 BBR可以改善糖尿病机体的GH/IGF-Ⅰ轴异常并且可以缓解胰岛素抵抗作用,改善机体糖代谢紊乱并对微血管病变起到保护作用。

Objective Study the effect of berberine( BBR) on GH/IGF-Ⅰ axis of diabetic rats induced by streptozotocin( STZ) and its mechanism. Methods 48 male Sprague-Dawley rats were randomly divided into normal control group( NC),diabetic group( DC),insulin treatment group( INS),and berberine( BBR) treatment group.There was no special treatment in NC group,no special treatment after STZ induction in DC group,subcutaneous injection of moderate effect insulin in INS group after induction by STZ,and intra-gastric administration of BBR after STZ induction in BBR group. The above four experiments were lasted for 8 weeks.Blood glucose and body weight of tail tip were monitored during the experiment. Serum GH and IGF-Ⅰ,were detected by enzyme immunoassays.Expression of GH gene in pituitary and IGF-Ⅰ,IGFBP-3,GHR gene in liver were detected by PCR technique. Results The blood glucose of DC group maintained a high level during the treatment.The difference of blood glucose between the INS group and NC group was statistically significant after the treatment.After treatment,the blood glucose level in BBR group was significantly different from that in NC group and DC group.The expression of GH gene( mRNA) in pituitary tissue of DC group was significantly higher than that of NC group. And the expression of GH gene in INS group and BBR group decreased after the treatment. The expression of GHR in liver of DC group was significantly decreased,and the expression of GHR in INS group and BBR group was up-regulated after treatment.The expression of IGFBP-3 in DC group was significantly decreased,and the expression of IGFBP-3 in INS group and BBR group was partially up-regulated after treatment.Conclusions The BBR could improve the abnormal of GH/IGF-Ⅰ of the diabetic body and could relieve the insulin resistance,improve the glucose metabolism disorder of the body,and play a protective role on the microangiopathy.