高山红景天干预对实验性糖尿病视网膜病变核因子κ B 调控多聚（ADP-核糖）聚合酶机制的影响。
Effect of the regimen of Gaoshan Hongjingtian on the mechanism of poly (ADP-ribose) polymerase regulation of nuclear factor kappa B in the experimental diabetic retinopathy.
机构信息
Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing, 100730, China.
出版信息
Chin Med J (Engl). 2013;126(9):1693-9.
BACKGROUND
Poly(ADP-ribose) polymerase (PARP) plays an important role in the death of retinal capillary cells in diabetic retinopathy (DR) partly via its regulation of nuclear factor kappa B (NF-κB). The current study investigated the effect of the regimen of Gaoshan Hongjingtian (RG) on the mechanism of PARP regulation of NF-κB, and demonstrated the possible impact of the RG and Gaoshan Hongjingtian (Rhodiola sachalinensis, RS) on diabetic retinopathy.
METHODS
Wistar rats were made diabetic by administering streptozotocin. They were then assigned to three groups at random. After 2 months, the three groups of these diabetic rats were treated with RS or RG, or untreated. Analyses of expression levels of PARP, NF-κB, and intercellular adhesion molecule-1 (ICAM-1) in the retinas of rats in different groups were performed by Western blotting and immunohistochemical assays, and mRNA levels of NF-κB and ICAM-1 were determined by real-time polymerase chain reaction (PCR). In addition, the basement membranes of capillaries in the rats' retinas were observed using electron microscopy, and diabetes-induced capillary degeneration (ghost pericytes and acellular capillaries) were quantitated.
RESULTS
From the third month after the injection of streptozotocin, the diabetic rats were given daily RG, RS or tap water separately. The diabetic rats failed to gain weight compared with normal age-matched rats, whereas their glycated hemoglobin levels were significantly increased. After 5 months, the mRNA levels of NF-κB and ICAM-1 and the protein expression of PARP, NF-κB, and ICAM-1 were significantly increased in the retinas of diabetic rats in the untreated group compared with the nondiabetic controls. After 8 months, the number of degenerated retinal capillaries (ghost pericytes and acellular capillaries) was significantly increased in the diabetic rats in the untreated group compared with normal age-matched rats. RG and RS inhibited diabetes-induced over-expression of PARP, NF-κB, and ICAM-1 in the retinas of diabetic rats at the end of 5-month diabetic duration. Treatment using RG and RS significantly inhibited increases in the number of acellular capillaries and pericyte ghosts and suppressed the basement membrane thickening in the retinas of rats with diabetes for 8 months compared with the control diabetic rats.
CONCLUSIONS
These results indicate that PARP plays an important role in the pathogenesis of diabetic retinopathy. RS and RG may have acted on the mechanism of PARP regulation of NF-κB, which suppressed the expression of NF-κB and ICAM-1, and led to the inhibition of retinal capillary degeneration.
背景
多聚（ADP-核糖）聚合酶（PARP）在糖尿病性视网膜病变（DR）中通过调节核因子 kappa B（NF-κB）部分发挥作用，导致视网膜毛细血管细胞死亡。本研究探讨了高山红景天（RG）方案对 PARP 调节 NF-κB 机制的影响，并证明了 RG 和高山红景天（Rhodiola sachalinensis，RS）对糖尿病性视网膜病变的可能影响。
方法
Wistar 大鼠经链脲佐菌素（STZ）诱导糖尿病，随机分为 3 组，2 个月后，3 组糖尿病大鼠分别给予 RS 或 RG 或不治疗。采用 Western blot 和免疫组化法检测各组大鼠视网膜中 PARP、NF-κB 和细胞间黏附分子-1（ICAM-1）的表达水平，实时聚合酶链反应（PCR）检测 NF-κB 和 ICAM-1 的 mRNA 水平。此外，用电子显微镜观察大鼠视网膜毛细血管基底膜，定量分析糖尿病诱导的毛细血管退行性变（鬼影细胞和无细胞毛细血管）。
结果
自 STZ 注射后第 3 个月起，糖尿病大鼠每天分别给予 RG、RS 或自来水。与同龄正常大鼠相比，糖尿病大鼠体重减轻，糖化血红蛋白水平显著升高。5 个月后，未治疗组糖尿病大鼠视网膜 NF-κB 和 ICAM-1 的 mRNA 水平及 PARP、NF-κB 和 ICAM-1 的蛋白表达均明显高于非糖尿病对照组。8 个月后，未治疗组糖尿病大鼠视网膜退化毛细血管（鬼影细胞和无细胞毛细血管）数量明显多于同龄正常大鼠。5 个月糖尿病病程结束时，RG 和 RS 抑制了糖尿病大鼠视网膜中 PARP、NF-κB 和 ICAM-1 的过度表达。与对照组糖尿病大鼠相比，RG 和 RS 治疗 8 个月可显著减少无细胞毛细血管和鬼影细胞的数量，抑制糖尿病大鼠视网膜基底膜增厚。
结论
这些结果表明，PARP 在糖尿病性视网膜病变的发病机制中起重要作用。RS 和 RG 可能作用于 PARP 调节 NF-κB 的机制，抑制 NF-κB 和 ICAM-1 的表达，从而抑制视网膜毛细血管退行性变。
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