内皮前体细胞自体移植促进缺血心肌血管的新生

目的:观察内皮前体细胞自体移植后能否促进血管新生、改善心肌灌注、进而改善心脏功能。方法:实验于2004-01/05在解放军总医院心内科实验室完成。①实验分组:雄性新西兰白兔32只,体质量3.0～3.5kg,随机分为治疗组和对照组,每组16只。②实验方法:治疗组自骨髓获取内皮前体细胞培养扩增。结扎动物冠状动脉前降支根部。心电图检测至少5个胸前导联出现ST段显著抬高作为模型制作成功标志。2.5g/L胰蛋白酶消化细胞,洗涤干净后5mL磷酸盐缓冲液悬浮细胞,结扎前降支2h后将细胞悬液从耳静脉注入动物体内,移植细胞数量为(9.8±2.9)×106个/只。对照组注射磷酸盐缓冲液5mL。饲养5周。③实验评估:分别行超声心动图检查和左心室压力曲线检测心脏功能和心肌组织的梗死情况以及通过免疫组织化学检测观察血管密度。结果:纳入新西兰白兔共32只,因前降支细小排除2只。对照组因心功能衰竭和腹泻各死亡1只。治疗组结扎前降支后突发室性心律失常死亡1只。最终27只进入实验。①体外培养的内皮前体细胞生长迅速,能够在2～3周达到预定移植细胞数量。②内皮前体细胞移植5周后,超声心动图检测显示治疗组动物心肌功能指数显著降低(P<0.01),左心室射血分数显著高于对照组(P<0.01),左心室舒张末压明显低于对照组(P<0.05),而等容收缩期左室压力最大上升速率显著升高(P<0.05)。③治疗组心肌梗死面积显著减小(P<0.01),而血管密度明显高于对照组(P<0.01)。④标记细胞主要位于梗死心肌组织,大部分整合至毛细血管中,参与血管新生。结论:内皮前体细胞自体移植能促进缺血心肌血管新生,有效改善缺血心肌的灌注,进而改善心脏功能。     

血管内皮生长因子对梗阻性肾病中肾小管周围毛细血管的调节作用

目的:观察刚断乳雄性SD大鼠单侧输尿管完全梗阻模型中血管内皮生长因子对肾小管周围毛细血管形态学变化的调节作用,探讨血管内皮生长因子在肾病进展中的生物活性作用。方法:实验于2005-03/2006-05在苏州大学儿科研究所完成。①实验材料:30只清洁级刚断乳雄性SD大鼠,体质量50～70g。②实验过程:结扎SD大鼠左侧输尿管建立单侧输尿管完全梗阻模型。于术后0,1,7,14,28d,分别随机选择6只模型大鼠,收获肾脏标本。③实验评估:采用苏木精-伊红染色观察肾积水的严重程度;Masson染色观察肾小管间质纤维化程度;PAS染色观察肾小管萎缩程度;免疫组织化学方法检测肾小管周围毛细血管的密度和血管内皮生长因子的表达水平;原位末端标记法对肾小管周围毛细血管和肾小管上皮细胞进行原位凋亡测定;透射电镜显示超微结构变化;血管内皮生长因子蛋白的表达强度和间质纤维化程度采用Leica图像分析系统检测。结果:①梗阻第1周,肾小管上皮细胞胞浆里的血管内皮生长因子染色在局部有增强,胎肝激酶1阳性肾小管周围毛细血管数量变化不显著,肾小管上皮细胞凋亡很少见,间质纤维化轻。第2,4周,血管内皮生长因子表达逐渐下降,直至在一些肾小管内完全消失。与此同时,胎肝激酶1阳性的肾小管周围毛细血管数量减少,肾小管扩张或萎缩明显,间质纤维化严重。②电镜显示肾小管上皮细胞、肾小管周围毛细血管内皮细胞的死亡形式主要为凋亡。③原位末端标记法显示肾小管上皮细胞凋亡在第14天达到高峰,然后迅速下降。④在梗阻第2周时,原位末端标记法阳性的肾小管周围毛细血管内皮细胞数与血管内皮生长因子表达面积百分比负相关(r=-0.668,P<0.05);肾小管周围毛细血管密度与血管内皮生长因子表达面积百分比正相关(r=0.707,P<0.05),而与肾小管上皮细胞凋亡负相关(r=-0.863,P<0.01)。结论:肾小管周围毛细血管减少与肾小管上皮细胞内血管内皮生长因子的表达不足相关,并与肾小管上皮细胞凋亡相关。     

The Impact of Iodine Concentration Disorders on Health and Cancer

Iodine deficiency is an ongoing problem. The implementation of salt iodization has significantly reduced the effects of iodine deficiency worldwide in recent years, and the remaining iodine deficiency is mild to moderate. Iodine is an essential substrate for the synthesis of thyroid hormones in the thyroid gland. It can also act as an antioxidant, as well as an anti-proliferative and pro-apoptotic factor. Pregnant women, breastfeeding women, and children are particularly affected by iodine deficiency. It leads to thyroid diseases and metabolic and developmental disorders, as well as cancer. However, an excessive iodine intake may, similarly to iodine deficiency, lead to the development of goiter, and toxic amounts of iodine can lead to thyroiditis, hyperthyroidism, and hypothyroidism, and even to the development of papillary thyroid cancer. Correcting iodine deficiency potentially reduces the chance of developing malignancies. Additional research is needed to better understand both the effect of iodine on carcinogenesis and the clinical outcome of iodine deficiency compensation on cancer patients’ prognosis. The upcoming public health challenge appears to be reducing salt consumption, which could result in a lower iodine intake. Thus, an iodine enrichment vehicle other than salt could be considered if salt iodine levels are not increased to compensate, and urine iodine levels should be monitored more frequently.