目的：探讨芍药苷调控磷脂酰肌醇-3激酶/蛋白激酶B(PI3K/Akt)信号通路对糖尿病视网膜病变大鼠炎症反应的影响。

方法：选取SPF级雄性SD大鼠70只，随机选择12只大鼠作为对照组(生理盐水灌胃)，余58只大鼠采用高糖高脂饮食联合腹腔注射链脲佐菌素(STZ)法构建糖尿病大鼠模型。将造模成功的糖尿病视网膜病变大鼠48只随机分为模型组(生理盐水灌胃)、芍药苷低剂量组(100 mg/kg芍药苷灌胃)、芍药苷高剂量组(200 mg/kg芍药苷灌胃)、二甲双胍组(100 mg/kg二甲双胍灌胃)，每组12只。比较各组大鼠体质量； HE染色观察大鼠视网膜组织病理学变化； 全自动生化仪检测大鼠空腹血糖、糖化血红蛋白、血清高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)、总胆固醇、甘油三酯水平； 酶联免疫吸附法检测大鼠血清超氧化物歧化酶(SOD)、活性氧(ROS)、丙二醛(MDA)、谷胱甘肽过氧化物酶(GSH-PX)、肿瘤坏死因子-α(TNF-α)、白介素-6(IL-6)、白介素-1β(IL-1β)\〗水平； Western blot检测大鼠视网膜组织紧密连接蛋白-1(ZO-1)、闭合蛋白(Occludin)、血管内皮钙黏蛋白(VE-Cadherin)、磷酸化PI3K(p-PI3K)、磷酸化Akt(p-Akt)表达。

结果：芍药苷低剂量组、芍药苷高剂量组大鼠Occludin、ZO-1、VE-Cadherin表达水平高于模型组，血清TNF-α、IL-6、IL-1β水平、p-PI3K、p-Akt蛋白表达水平低于模型组，且芍药苷高剂量组明显优于芍药苷低剂量组(均P<0.05)。

结论： 芍药苷可能通过抑制PI3K/Akt信号通路来减轻糖尿病视网膜病变大鼠炎症反应。

METHODS: A total of 70 SPF male SD rats were selected, and 12 rats were randomly selected as the control group(normal saline gavage). The remaining 58 rats were fed with high-sugar and high-fat diet combined with intraperitoneal injection of streptozotocin(STZ)to establish diabetic rat models. Rats with diabetic retinopathy were randomly divided into model group(normal saline), paeoniflorin low-dose group(100 mg/kg paeoniflorin), paeoniflorin high-dose group(200 mg/kg paeoniflorin)and metformin group(100 mg/kg metformin), with 12 rats in each group. The body mass of the rats in each group were compared. HE staining was used to observe the pathological changes of the rat retina. Automatic biochemical analyzer was used to detect the levels of fasting blood glucose, glycosylated hemoglobin, serum high-density lipoprotein cholesterol(HDL-C), low-density lipoprotein cholesterol(LDL-C), total cholesterol and triglyceride in the rats. Enzyme-linked immunosorbent assay was used to detect the levels of serum superoxide dismutase(SOD), reactive oxygen species(ROS), malondialdehyde(MDA), glutathione peroxidase(GSH-PX), tumor necrosis factor-α(TNF-α), interleukin-6(IL-6)and interleukin-1β(IL-1β)in the rats. Western blot was used to detect the expressions of Occludin, p-PI3K, tight junction protein-1(ZO-1), p-Akt and VE-Cadherin in the rat retina.

RESULTS: The expression levels of Occludin, ZO-1 and VE-cadherin in low-dose and high-dose paeoniflora groups were higher than those in the model group, while the expression levels of TNF-α, IL-6, IL-1β, p-PI3K and p-Akt in serum were lower than those in the model group. The high-dose group of paeoniflorin was significantly better than the low-dose group of paeoniflorin(all P<0.05).

CONCLUSION: Paeoniflorin may reduce inflammatory response in diabetic retinopathy rats by inhibiting PI3K/Akt signaling pathway.