摘要
目的以脑组织核因子-κB(NF-κB)表达和血清肿瘤坏死因子-α(TNF-α)为判断标准,探讨家兔糖尿病模型胰岛素(Ins)用药治疗的适宜方案。方法40只雄性家兔随机分成5组[对照组(N组)、模型组(D组)、多次Ins治疗组(A组)、50R预混Ins治疗组(B组)、30R预混Ins治疗组(C组)]。其中,4组用四氧嘧啶制作成家兔糖尿病模型。治疗组用Ins30d后处死动物,同时处死其他组动物;记录各治疗组血糖达标时间及达标时Ins用量。观察比较各组血糖、脑组织含水量、脑组织核转录因子-κB(NF-κB)肿瘤坏死因子-α(TNF-α)、大脑顶叶组织片病理学变化。结果B组的达标Ins用量较A、C组少,C组达标时Ins用量最多,差异有统计学意义(P<0.01)。A组达标时间最短(7.00±1.31)d、C组血糖达标时间最长(19.63±1.41)d,各组间差异有统计学意义(P<0.01)。实验结束时,治疗组空腹血糖、HbA1c、TNF-α较D组下降,差异有统计学意义(P<0.05);NF-KB灰度值较D组增高(P<0.05);脑组织含水量A组明显升高,差异有统计学意义(P<0.05)。治疗组脑组织含水量、TNF-α与血糖呈负相关(r=-0.44、-0.77;P<0.05);脑NF-κB灰度值与血糖呈正相关(r=0.52;P<0.01)。模型组脑组织含水量、脑NF-κB灰度值与血糖呈负相关(r=-0.81、-0.86;P<0.05);TNF-α与血糖呈正相关(r=0.79,P<0.02)。大脑顶叶皮质锥体细胞组织水肿及病变受损严重程度D>A>B>C。结论30R预混胰岛素治疗方案最佳。提供1个较高的基础胰岛素浓度加少量餐时胰岛素峰值量治疗糖尿病,血糖平稳缓降,对糖尿病神经组织有治疗和保护作用。多次胰岛素3短加1中或长的强化治疗及太短时间达标的方法不可首选。
【Objective】To investigate the optimal insulin regimens on Rabbit Diabetes Mellitus Model according to expression of nuclear factor kappa B （NF-κB） in the brain tissue and the level of tumor necrosis factor-alpha （TNF-α）.【Methods】40 alone male rabbits were divided random into 5 group [control group （N group）,model group （D group）,A group received multiple subcutaneous injection of insulin,B group adopted isophane protamine biosynthetic human injection （pre-mixed 50R）,C group received isophane protamine biosynthetic human injection （premixed 30R）.Homemade rabbit Diabetes Mellitus Models induced by Alloxan were divided into 4 groups.After 30 day,therapy group to inject insulin treatment were sacrifeced.Other group animal were died at the same time.We observed the blood glucose levels,the water content of the brain,TNF-α,the parietal lobe tissue of the brain and analysed the expression of NF-κB in the brain tissue by immunohistochemistry.The value of inspected was comparied to that of untreated group and control groups.【Results】Insulin dose of B group is less than A group and C group.C group used the largest amount of insulin to get to the targeted blood glucose levels.There was significant difference among 3 groups （P 〈0.01）.The period was Shortest in A group （7.00 ± 1.31 days） and longest in C group （19.63 ± 1.41 days）.There was significant difference among 3 groups （P 〈0.001）.At the end of the investigation,blood-fasting,HbA1c,TNF-α were descend;gray scale of NF-KB was heighten in treatment group.the water content of the brain was obviously high in A group.There was statistical significance in difference （P 〈0 01）.The blood glucose were positively related to the water content of the brain,but negatively related to TNF-α （r =-0.44,-0.77,P 〈0.05）,the blood glucose were positively related to the NF-κB gradation value （r =0.52;P 〈0.01） in insul in therapy group;The blood glucose were negatively related to the water content of the brain,and negatively related to the NFκB gradation value （r =-0.81,-0.86;P 〈0.05）;but positively related to TNF-α （r =0.79,P 〈0.02） in modle group.The severe and damage on kidney and expression of the inflammatory factors were D 〉 A 〉 B 〉 C.【Conclusions】 Subcutaneous injection of pre-mixed 30R may be the optimal insulin treatment protocols.This regimen supplies more basal insulin and less bolus insulin.The blood glucose drops steadily and the diabetic kidney can be protected.The regimen of intensive insulin therapy by multiple subcutaneous injection （triple daily injections Short-acting insulin and once injection of intermediate-acting insulin or long-acting insulin daily） and reaching the target blood glucose quickly should not be used as a primary regimen.
出处
《中国现代医学杂志》
CAS
CSCD
北大核心
2009年第24期3713-3717,共5页
China Journal of Modern Medicine
基金
广西壮族自治区科学技术厅自然科学基金课题(桂科基0385005)
