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


CONCLUSIONS
TMP injection partially protects against MNU-induced retinal damage by upregulating the nuclear translocation of p65 to inhibit photoreceptor cells apoptosis.
Yang
Jin-Nan
JN
School of Pharmacy, Xinxiang Medical College, Xinxiang 453003, China. jinnan1@126.com
Chen
Jin-Mao
JM
Luo
Lin
L
Lin
Shao-Chun
SC
Li
Dai
D
Hu
Shi-Xing
SX
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002467:Cell Nucleus / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism; D005260:Female; D020672:I-kappa B Proteins / Q000378:metabolism; D030004:Ligusticum / Q000737:chemistry; D008770:Methylnitrosourea; D000072000:NF-KappaB Inhibitor alpha; D020419:Photoreceptor Cells, Vertebrate / Q000378:metabolism / Q000473:pathology*; D010946:Plants, Medicinal / Q000737:chemistry; D011719:Pyrazines / Q000302:isolation & purification / Q000494:pharmacology*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012164:Retinal Diseases / Q000139:chemically induced / Q000473:pathology; D051996:Transcription Factor RelA / Q000378:metabolism*
D020672:I-kappa B Proteins; C000606206:Nfkbia protein, rat; D011719:Pyrazines; D051996:Transcription Factor RelA; D000072000:NF-KappaB Inhibitor alpha; D008770:Methylnitrosourea; C017953:tetramethylpyrazine