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川芎嗪通过调节核因子-κB的核转位保护大鼠光感受器细胞。

Tetramethylpyrazine protected photoreceptor cells of rats by modulating nuclear translocation of NF-kappaB.

作者信息

Yang Jin-Nan, Chen Jin-Mao, Luo Lin, Lin Shao-Chun, Li Dai, Hu Shi-Xing

机构信息

School of Pharmacy, Xinxiang Medical College, Xinxiang 453003, China.

出版信息

Acta Pharmacol Sin. 2005 Jul;26(7):887-92. doi: 10.1111/j.1745-7254.2005.00141.x.

DOI:10.1111/j.1745-7254.2005.00141.x
PMID:15960898
Abstract

AIM

To evaluate the effect of tetramethylpyrazine (TMP) injection on retinal damage induced by N-methyl-N-nitrosourea (MNU) in rats and on nuclear factor-kappa B (NF-kappaB) family members.

METHODS

Female Sprague-Dawley (SD) rats were randomly divided into groups: (i), control group; (ii), model group; and (iii), TMP-injection groups, in which the rats were subdivided into 40 mg/kg, 80 mg/kg and 160 mg/kg groups. Drugs were injected ip into 47-day-old SD rats once a day. At 50 days of age, all rats in the model group and drug groups also received a single ip injection of 60 mg/kg MNU. Rats in group 1 received ip injection of physiological saline. All rats were killed at different times after MNU or physiological saline treatment. The apoptotic index of photoreceptor cells was calculated by TUNEL labeling; retinal damage was evaluated based on retinal thickness and the expression of NF-kappaB family members was detected by Western blot.

RESULTS

TMP injections, in a dose-dependent manner, suppressed photoreceptor cell apoptosis and decreased its loss in the peripheral retina. As compared with the MNU-treated group, TMP injection at a dose of 160 mg/kg also time-dependently upregulated the NF-kappaB/p65 protein level in the nucleus and downregulated the IkappaBalpha protein level in the cytoplasm. However, no protective effect of TMP injection on MNU-induced central retinal damage was found.

CONCLUSION

TMP injection partially protects against MNU-induced retinal damage by upregulating the nuclear translocation of p65 to inhibit photoreceptor cells apoptosis.

摘要

目的

评估川芎嗪(TMP)注射液对N-甲基-N-亚硝基脲(MNU)诱导的大鼠视网膜损伤及核因子-κB(NF-κB)家族成员的影响。

方法

将雌性Sprague-Dawley(SD)大鼠随机分为几组:(i)对照组;(ii)模型组;(iii)TMP注射组,其中大鼠再细分为40mg/kg、80mg/kg和160mg/kg组。每天经腹腔注射药物给47日龄的SD大鼠。在50日龄时,模型组和药物组的所有大鼠也经腹腔注射一次60mg/kg的MNU。第1组大鼠经腹腔注射生理盐水。在MNU或生理盐水处理后的不同时间处死所有大鼠。通过TUNEL标记计算光感受器细胞的凋亡指数;根据视网膜厚度评估视网膜损伤,并通过蛋白质免疫印迹法检测NF-κB家族成员的表达。

结果

TMP注射以剂量依赖性方式抑制光感受器细胞凋亡,并减少其在外周视网膜中的损失。与MNU处理组相比,160mg/kg剂量的TMP注射还能时间依赖性地上调细胞核中NF-κB/p65蛋白水平,并下调细胞质中IκBα蛋白水平。然而,未发现TMP注射对MNU诱导的视网膜中央损伤有保护作用。

结论

TMP注射通过上调p65的核转位来抑制光感受器细胞凋亡,从而部分预防MNU诱导所致的视网膜损伤。

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