不同 N-乙醜-5-经色胺(NAS)给药途径对大鼠视网膜缺血- 再灌注损伤的影响

Objective To investigate the changes of histopathological features, expression of active Caspase-3 protein and cell apoptosis in rats with retina ischemia-reperfusion injury (RIRI) by two different administration routes of Nacetylserotonin (NAS), intraperitoneal injection and tail intravenous injection. Methods Totally 54 healthy adult male Sprague-Dawley rats were divided into normal control group (n=6), RIRI intraperitoneal group (n=12), RIRI intravenous group (n=12), NAS intraperitoneal group (n=12) and NAS intravenous group (n=12) by random number table method. RIRI models were established by ocular hypertension method. Rats in NAS intraperitoneal group and NAS intravenous group respectively received intraperitoneal injection and tail intravenous injection of NAS (10 mg·kg^-1) 30 minutes before modeling, and rats in RIRI intraperitoneal group and RIRI intravenous group respectively received intraperitoneal injection and tail intravenous injection of same amount of normal saline 30 minutes before modeling. Twenty-four hours after RIRI, the expression of active Caspase-3 in retina was detected by immunohistochemical staining, and the apoptosis of retinal cells was detected by TUNEL staining. Seven days after RIRI, the histopathological changes of retina were observed by HE staining. Results HE staining showed that the retinal cells at each layer were orderly and regularly arranged for rats in normal control group; 7 days after RIRI, the retinal cells for rats in RIRI intraperitoneal and intravenous groups were sparsely and disorderly arranged, irregular in shape, and thinner in the inner retinal layer; the retinal cells in the NAS intraperitoneal group were regularly and orderly arranged; NAS intravenous group had basically normal cell morphology and arrangement in each retinal layer. The thickness of retinal inner layer in the NAS intravenous group was (91.67±1.43) μm, which was significantly higher than (87.80±1.33) μm in NAS intraperitoneal group, (82.37±1.09) μm in RIRI intraperitoneal group and (82.81±0.90) μm in RIRI intravenous group, and statistical differences were found (all P<0.05). And the number of retinal ganglion cells in the NAS intravenous group was (616.90±79.51) mm^-2, which was significantly higher than (529.25±92.05) mm-2 in the NAS intraperitoneal group, (434.42±87.17) mm^-2 in RIRI intravenous group and (390.72±72.12) mm^-2 in RIRI intraperitoneal group, and statistical differences were found (all P<0.05). Immunohistochemical staining results showed: 24 hours after RIRI, the number of active Caspase-3 positive cells in the NAS intravenous group was (145.01±22.54) mm^-2, lower than (221.34±30.84) mm^-2 in the NAS intraperitoneal group (P<0.05), and both of which was significantly lower than (380.54±41.25) mm^-2 in the RIRI intravenous group and (387.79±26.72) mm^-2 in RIRI intraperitoneal group (all P<0.05). TUNEL staining showed: 24 hours after RIRI, the number of apoptotic cells in the NAS intravenous group was (1468.03±128.40) mm^-2, lower than (1968.96±254.98) mm^-2 in the NAS intraperitoneal group (P<0.05), and both of which was obviously lower than (2122.77±165.76) mm^-2 in the RIRI intravenous group and (2140.53±177.96) mm^-2 in the RIRI intraperitoneal group (all P<0.05). Conclusion Both intraperitoneal and intravenous injection of NAS can reduce retinal cell apoptosis thereby relieving retinal damage in RIRI rats. Intravenous administration is more effective than intraperitoneal administration.