摘要目的 观察前列地尔对糖尿病大鼠视网膜组织细胞凋亡相关基因Bcl-2和Bax表达的影响,探讨前列地尔防治糖尿病性视网膜病变的作用机制。 方法 选择健康成年SD大鼠40只,随机分成正常对照组、模型组、前列地尔低剂量(0.5 μg/kg)组和高剂量(1 μg/kg)组。腹腔内注射链脲佐菌素(STZ)诱发大鼠糖尿病。前列地尔治疗组给予前列地尔静脉注射4周,模型组和对照组灌服等体积生理盐水,随后进行视网膜组织取材,采用Real Time PCR 法检测Bcl-2和Bax的mRNA表达,采用Western Blot法检测Bcl-2和Bax的蛋白表达。 结果 1)Bcl-2 mRNA和蛋白表达结果模型组(0.42±0.05、0.33±0.03)均显著高于对照组(0.37±0.11、0.28±0.03)(P<0.05);前列地尔低剂量组(0.56±0.06、0.46±0.04)、高剂量组(0.65±0.04、0.59±0.04)均显著高于模型组(0.42±0.05、0.33±0.03),且与剂量呈正相关(P<0.05);2)Bax mRNA 和蛋白表达结果模型组(0.75±0.27、0.71±0.04)均显著高于对照组(0.33±0.05、0.22±0.03)(P<0.05);前列地尔低剂量组(0.60±0.08、0.48±0.04)、高剂量组(0.44±0.07、0.31±0.02)均显著低于模型组(0.75±0.27、0.71±0.04),且与剂量呈负相关(P<0.05)。 结论 前列地尔可通过调节糖尿病大鼠视网膜组织中Bax和Bcl-2的表达改善视网膜基金项目河北省中医药管理局科研计划项目基金(2014104)作者简介张会岭(1970-),女,河北迁安人,本科学历,主治医师,主要从事临床眼科工作。通讯作者贾浩洋,E-mail2900090162@qq.com。特异性分别为40.00%和84.91%。故以临床经济学的观点来看,对重危新生儿应及早进行PCT检测以判断是否存在感染[8]。对PCT 阳性尤其是≥2 ng/ml 的重危患儿, 需高度怀疑全身性细菌感染,应尽早足量应用抗生素,在治疗过程动态观测PCT 水平,可判断疗效、指导预后。CRP水平分布显示,四组大部分病例集中在0~2 mg/L区间内,以2 mg/L为临界值,诊断感染的敏感性为42.32%,特异性为89.89%;其中诊断败血症的敏感性47.27%,特异性为69.82%;诊断局部感染的敏感性为40.86%,特异性为70.17%。诊断感染的敏感性和特异性均低于PCT,对败血症的诊断敏感性也明显低于0.5 ng/ml PCT。 这与其他研究者以外周血为标本得出的结论基本一致[9-11]。这可能与急性期时相蛋白在体内受影响因素较多有关[12]。CRP取更高临界值如10 mg/L时,敏感性过低,不宜考虑为理想的感染诊断指标水平。本研究表明,PCT和CRP都能不同程度地提示宫内感染。相比CRP,脐血PCT似乎是分娩时预测感染尤其是败血症的更佳炎症标志物,同时可以避免对新生儿进行有创采样并可能减少抗生素的使用,但它仍然不能代替临床观察成为确诊唯一依据,尚需更多的相关研究来更好地评估它的诊断价值。值得注意的是,在本研究中这两种炎症指标敏感性数值相对偏低,可能与新生儿胎内免疫系统不成熟炎症反应低下、分泌量少有一定关系,以这些指标评判感染时需特别避免漏诊。参考文献[1] 袁正泉,陈中湘,刘培香.血清降钙素原(PCT)测定对败血症早期诊断的临床意义[J].实用预防医学,2011,18(12)2394-2395.[2] 崔雪薇,薛辛东.新生儿败血症临床检测指标的研究进展[J].国际儿科学杂志,2015,42(2)177-179.[3] 常立文,李文斌.宫内感染与早产儿疾病[J].中华实用儿科临床杂志,2013,28(14)1041-1043.[4] 徐峰,冯泽蛟,陈文殊,等.妊娠合并感染性疾病的诊治对策分析[J].中华全科医学,2013,11(10)1528-1529.[5] 王瑾,张蓉,邵肖梅.降钙素原在新生儿感染中的应用价值[J].临床儿科杂志, 2005, 23(2)105-107.[6] 任艳丽,陈涵强. 降钙素原在早期诊断新生儿感染疾病的临床意义[J].中国新生儿科杂志,2009,24(1) 125-128.[7] 范颖,余加林.可预测早发型新生儿败血症的脐血标志物[J].儿科药学杂志,2012,18(1)49-52.[8] Guibourdenche J,Bedu A, Petzold L, et al .Biochemical markers of neonatal sepsis value of procalcitonin in emergency setting[J] .Ann Clin Biochem, 2002, 39(pt 2)130-135.[9] 李淑丽, 王北海, 孙和才, 等.降钙素原检测对新生儿败血症早期诊断治疗及病情评估的临床意义[J].中国医药导报,2011,8(1)26-27, 68.[10] 吕菊红, 马红茹, 李文君, 等.PCT和CRP测定在新生儿败血症早期诊断中的价值[J].中国妇幼健康研究,2012,23(4)463-465.[11] 聂翠华, 杜梦欣.86例新生儿败血症血清降钙素原和C反应蛋白的水平研究[J].检验医学与临床,2009,6(12)979-980.[12] Enguix A, Rey C, Concha A, et al .Comparison of procalcitonin with C- reaction protein and serum amyloid for the early diagnosis of bacterial sepsis in critically ill neonates and children[J] .Int Care Med, 2001, 27211-215.收稿日期2016-05-19病变。
Abstract：Objective To observe the effect of alprostadil on the expression of apoptosis-related genes, Bcl-2 and Bax in retinal tissues of diabetic rats, and to explore the mechanism of alprostadil for preventing and curing diabetic retinopathy. Methods Forty healthy adult SD rats were chosen and randomly divided into the control group, the model group, alprostadil low-dose group (0.5 ug/kg) and alprostadil high-dose group (1 ug/kg). Diabetic mellitus was induced by intraperitoneal injection of streptozotocin (STZ). The rats in alprostadil-treated groups had intravenous drip with alprostadil solution for 4 weeks, while those in the control group were given the same volume of saline by gavage. Retinal tissues of all the rats were sampled. Real-time polymerase chain reaction was used to detect the mRNA expression of Bcl-2 and Bax, and Western Blot assay to determine the protein expression of Bcl-2 and Bax. Results The expression levels of Bcl-2 mRNA and protein in retina in the model group were significantly higher than those of the control group ((0.42±0.05) vs. (0.37±0.11), (0.33±0.03) vs. (0.28±0.03), (P<0.05)). The expression levels of Bcl-2 mRNA and protein in retina in alprostadil low-dose group ((0.56±0.06), (0.46±0.04)) and alprostadil high-dose group ((0.65±0.04), (0.59±0.04)) were significantly higher than those of the model group ((0.42±0.05), (0.33±0.03)), and shown a positive correlation with the dose of alprostadil (P<0.05). The expression levels of Bax mRNA and protein in retina in the model group were significantly higher than those of the control group ((0.75±0.27) vs. (0.33±0.05), (0.71±0.04) vs. (0.22±0.03), (P<0.05)). The expression levels of Bax mRNA and protein in retina in alprostadil low-dose group ((0.60±0.08), (0.48±0.04)) and alprostadil high-dose group ((0.44±0.07), (0.31±0.02)) were significantly lower than those of the model group ((0.75±0.27), (0.71±0.04)), and shown a negative correlation with the dose of alprostadil (P<0.05). Conclusions Alprostadil may improve diabetic retinopathy by regulating the expression of Bcl-2 and Bax in retina tissues of diabetic rats.
张会岭, 张春阳, 晁英, 刘晓曼, 贾浩洋. 前列地尔对糖尿病大鼠视网膜Bcl-2、Bax表达的影响[J]. 实用预防医学, 2016, 23(12): 1519-1522.
ZHANG Hui-ling, ZHANG Chun-yang, CHAO Ying, LIU Xiao-man, JIA Hao-yang. Effect of alprostadil on the expression of Bax and Bcl-2 in retinal tissues of rats with diabetic mellitus. , 2016, 23(12): 1519-1522.
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