大黄?虫丸对p53介导的信号通路调控糖尿病大鼠视网膜周细胞凋亡的研究
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摘要
目的:探讨大黄?虫丸对p53介导的信号通路调控糖尿病大鼠视网膜周细胞凋亡的作用与机理。方法:将Wistar雄性大鼠随机分为正常对照组、模型对照组、大黄?虫丸低剂量组、中剂量组和高剂量组5组。除空白组外各组均采用链佐脲菌素腹腔注射诱导DR大鼠模型。造模成功后分别于给药6周、12周后取大鼠眼球,通过免疫组织化学联合免疫荧光染色法及Western blot法分别定位定量检测p53、MDM2在视网膜组织中的表达。结果:与模型组比较,大黄?虫丸组p53表达下调、MDM2上升(均P <0. 05)。结论:大黄?虫丸可能通过维持p53、MDM2二者间的精细平衡,抑制周细胞的凋亡,发挥防治糖尿病视网膜病变微血管损伤的作用。
Objective: To explore the mechanism of Dahuang Zhechong Pills on p53 mediated signal transduction pathway in diabetic rat retinal pericytes apoptosis. Methods: Totally 100 male SPF Wistar male rats were randomly divided into blank group,model group,Dahuang Zhechong Pills low dose group,middle dose group and high dose group. Except the blank group,DR rats were induced by intraperitoneal injection of streptozotocin in each group. After successful modeling,rats' eyes were taken out after6 and 12 weeks respectively. The expressions of p53 and MDM2 in retinal tissue were detected by immunohistochemistry combined with immunofluorescence staining and Western blot methods. Results: Compared with the model group,Dahuang Zhechong Pills group decreased expression of p53 and increased MDM2( P < 0. 05). Conclusion: Dahuang Zhechong Pills may be effective by balancing p53 and MDM2 between the two,inhibiting the apoptosis of pericytes play,microvascular injury prevention and treatment of diabetic retinal lesions.
Objective: To explore the mechanism of Dahuang Zhechong Pills on p53 mediated signal transduction pathway in diabetic rat retinal pericytes apoptosis. Methods: Totally 100 male SPF Wistar male rats were randomly divided into blank group,model group,Dahuang Zhechong Pills low dose group,middle dose group and high dose group. Except the blank group,DR rats were induced by intraperitoneal injection of streptozotocin in each group. After successful modeling,rats' eyes were taken out after6 and 12 weeks respectively. The expressions of p53 and MDM2 in retinal tissue were detected by immunohistochemistry combined with immunofluorescence staining and Western blot methods. Results: Compared with the model group,Dahuang Zhechong Pills group decreased expression of p53 and increased MDM2( P < 0. 05). Conclusion: Dahuang Zhechong Pills may be effective by balancing p53 and MDM2 between the two,inhibiting the apoptosis of pericytes play,microvascular injury prevention and treatment of diabetic retinal lesions.
引文
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[11]郭承伟,张宏国,马栋.从络论治糖尿病视网膜病变的理论与应用探讨[J].中国中医眼科杂志,2011,22(5):8-10.
[2]Miller A G,Smith d G,Bhat m,et al.Glyoxalase I is critical for human retinal capillary pericyte survival under hyperglyeemie conditions[J].J Biol Chem,2006,28(17):11864-11871.
[3]Vousden KH.p53 in health and disease[J].Nat Rev Mol Cell Biol,2007(4):275-283.
[4]马栋,王静波,郭承伟,等.络治法对STZ诱导的糖尿病大鼠视网膜NF-KB表达的影响[J].中国中医眼科杂志,2015,25(2):82-86.
[5]徐叔云,卞如濂,陈修,等.药理实验方法学[J].3版.北京:人民卫生出版社,1982:附录.
[6]Smith S W,Chand S,Savage C O.Biology of the renal pericyte[J].Nephrol Dial Transplant,2012,27(6):2149-2155
[7]Deben C,Wouters A,Op de Beeck K,et al.The MDM2-inhibitor Nutlin-3 synergizes with cisplatin to induce p53 dependent tumor cell apoptosis in non-small cell lung cancer[J].Oncotarget,2015,6(26):22666-22679.
[8]Zheng T,Wang J,Zhao Y,et al.Spliced MDM2 isoforms promote mutant p53 accumulation and gain of function in tumorigenesis[J].Nat Commun,2013,4:2996.
[9]Mendoza M,Mandani G,Momand J.The MDM2 gene family[J].Biomol Concepts,2014,5(1):9-19.
[10]Bose I,Ghosh B.The P53-MDM2 network from oscillations to apoptosis[J].J Biosci,2007,32(5):991-997.
[11]郭承伟,张宏国,马栋.从络论治糖尿病视网膜病变的理论与应用探讨[J].中国中医眼科杂志,2011,22(5):8-10.