Zhang Qian, Xiao Xinhua, Zheng Jia, Li Ming, Yu Miao, Ping Fan, Wang Tong, Wang Xiaojing
Key Laboratory of Endocrinology, Translational Medicine Center, Ministry of Health, Department of Endocrinology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China.
Front Physiol. 2018 Oct 24;9:1501. doi: 10.3389/fphys.2018.01501. eCollection 2018.
Diabetic retinopathy (DR) is a severe microvascular complication of diabetes. Previous clinical trials have shown that Compound Danshen Dripping Pill (CDDP) improves DR symptoms. However, the mechanism involved remains unclear. Rats fed a high-fat diet and injected with streptozotocin (STZ) were used as an experimental type 2 diabetes rodent model. CDDP was administered to two groups of diabetic rats at 0.2 and 0.4 g/kg/day via gastric gavage for 12 weeks. After the 12 weeks of treatment, retinal function was evaluated by electroretinography (ERG). Histological staining and TdT-mediated dUTP nick-end labeling (TUNEL) assays were also performed. Retinal genome expression was determined by gene array. We found that CDDP moderated ERG and histological abnormalities in diabetic rats, independent of blood glucose level. A gene array showed that CDDP changed 262 genes significantly in the diabetic retina. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis indicated that differentially expressed genes in the CDDP-treated groups were involved mainly in the apoptosis pathway. Moreover, CDDP reduced the number of TUNEL-positive cells in the diabetic retinas. CDDP prevented the reduction in Bcl-2 expression and the increase in BCL-2 associated X (Bax) and caspase-3 (Casp3) expression in diabetic rats. Our results suggest that CDDP exerts its neuroprotective functions by inhibiting cell apoptosis in diabetic rats.
糖尿病视网膜病变（DR）是糖尿病严重的微血管并发症。以往的临床试验表明，复方丹参滴丸（CDDP）可改善DR症状。然而，其中涉及的机制仍不清楚。将喂食高脂饮食并注射链脲佐菌素（STZ）的大鼠用作实验性2型糖尿病啮齿动物模型。以0.2和0.4 g/kg/天的剂量通过灌胃法给两组糖尿病大鼠施用CDDP，持续12周。治疗12周后，通过视网膜电图（ERG）评估视网膜功能。还进行了组织学染色和TdT介导的dUTP缺口末端标记（TUNEL）分析。通过基因芯片测定视网膜基因组表达。我们发现，CDDP可减轻糖尿病大鼠的ERG和组织学异常，且与血糖水平无关。基因芯片显示，CDDP使糖尿病视网膜中的262个基因发生了显著变化。京都基因与基因组百科全书（KEGG）通路分析表明，CDDP治疗组中差异表达的基因主要参与凋亡通路。此外，CDDP减少了糖尿病视网膜中TUNEL阳性细胞的数量。CDDP可防止糖尿病大鼠中Bcl-2表达的降低以及BCL-2相关X蛋白（Bax）和半胱天冬酶-3（Casp3）表达的增加。我们的结果表明，CDDP通过抑制糖尿病大鼠的细胞凋亡发挥其神经保护作用。
