目的：通过测定经臭氧灌肠治疗后的糖尿病大鼠视网膜及血清中血管内皮生长因子(VEGF)、缺氧诱导因子-1α(HIF-1α)与色素上皮衍生因子(PEDF)的表达差异，了解臭氧在早期糖尿病视网膜病变治疗的作用。

方法： 选取70只雄性SD大鼠中的10只做为正常对照组，予以正常饮食； 余大鼠经适应性喂养后通过腹腔一次性注射链脲佐菌素(50mg/ml)制作糖尿病模型。将造模成功的大鼠模型随机分成模型对照组(B组)、氧气治疗组(C组)及臭氧治疗组(D组)，其中臭氧治疗组给予臭氧灌肠治疗(2次/wk，共计1mo)，氧气治疗组给予同等剂量及频次的氧气进行灌肠治疗，治疗1mo后取视网膜及血清，使用免疫组化法检测视网膜中VEGF的表达，使用ELISA及RT-PCR的方法检测视网膜及血清中VEGF、HIF-1α与PEDF的含量。

结果：免疫组化结果显示VEGF主要在内层视网膜表达，而臭氧治疗组VEGF表达接近于空白对照组； 血清与视网膜中VEGFmRNA表达在四组间均有统计学差异(F=23.923； P=0.000)，其中臭氧治疗组VEGF的表达接近于空白对照组，但差异仍有统计学意义(P<0.05)； 而模型对照组同氧气治疗组的VEGF表达亦无统计学差异(P>0.05)； 相对于空白对照组，臭氧治疗组HIF-1α表达下降(P<0.05)， 而在模型对照组与氧气治疗组间无统计学差异(P>0.05)。PEDFmRNA在四组间的表达均有差异，但差异均无统计学意义(P>0.05)。

结论：臭氧灌肠治疗可以有效的降低血清及视网膜中VEGF 和HIF-1α 的表达，可以一定程度的抑制早期糖尿病视网膜病变的发展。

AIM:To study vascular endothelial growth factor(VEGF), pigment epithelium derived factor(PEDF)and hypoxia inducible factor-1α(HIF-1α)expression in retinal and serum in ozone-treated streptozotocin(STZ)-induced diabetic rats and to determine the possible efficacy of ozone therapy for diabetic retinopathy(DR).

METHODS:Seventy male Sprague-Dawley rats were used. Group A(n=10)received a normal diet, diabetic molding established by intraperitoneal injection of STZ(50mg/ml), then divided into three groups, group B without any intervene; and groups C and D given oxygen and ozone clyster treatment respectively, twice per week for 1mo. Retina and blood were taken under general anesthesia. Reverse transcription-polymerase chain reaction(RT-PCR)and enzyme-linked immunosorbent assay(ELISA)methods were used to study retinal and serum VEGF, HIF-1α and PEDF expression.

RESULTS:VEGF occurred mostly in the inner layer of the retina; the difference of VEGF in the retina among each group has statistical difference(F=23.923; P=0.000); in which, group D closer to group A, but still has statistical difference(P<0.05); there is no difference between group B and C(P>0.05)except for no difference between group A and D(P>0.05), others as same result as retinal VEGF expression.HIF-1α expression decreased in ozone-treated rats(group D)compared with control group(P<0.05); the difference between group A and groups B and C was significant(P<0.05), and the difference between groups B and C with no statistical difference(P>0.05). Overall, PEDF expression was lower than VEGF and HIF-1α, and groups A and D showed more expression than groups B and C, but the differences were not significant(P >0.05).

CONCLUSION: Ozone administration can reduce the VEGF and HIF-1α expression and ozone may have potential uses in its treatment.

新疆维吾尔自治区自然科研基金(项目号:2014211C046)