【摘要】：目的：初步觀察核轉(zhuǎn)錄因子κB（nuclear factor-κB，NF-κB）抑制劑吡咯烷二硫代氨基甲酸鹽(pyrrolidine dithiocarbamic, PDTC）對(duì)全腦缺血再灌注(global cerebral ischemia reperfusion，GCIR)大鼠神經(jīng)元損傷的保護(hù)作用及其機(jī)制。 方法：采用夾閉兩側(cè)頸總動(dòng)脈20min合并全身低血壓的方法建立GCIR模型。通過Morris水迷宮進(jìn)行空間學(xué)習(xí)記憶能力的檢測(cè)，HE常規(guī)染色觀察大鼠海馬神經(jīng)元數(shù)目及形態(tài)的變化，RT-PCR檢測(cè)大鼠海馬環(huán)氧酶2（cyclooxygenase2, COX2）的mRNA表達(dá)，免疫組化檢測(cè)海馬NF-κB、COX2蛋白表達(dá)，ELISA測(cè)定大鼠海馬中前列環(huán)素（prostacyclin，PGI2）和血栓素A2（thromboxaneA2，TXA2）含量。 結(jié)果：與假手術(shù)組（sham）比較，GCIR大鼠的空間學(xué)習(xí)記憶能力顯著下降；海馬神經(jīng)元凋亡30min開始出現(xiàn)（P 0.05），7d達(dá)到高峰（P 0.05）；NF-κB蛋白表達(dá)30min時(shí)開始升高，，24h達(dá)到高峰，15d仍明顯高于假手術(shù)組（P 0.01）；COX2mRNA表達(dá)2h時(shí)開始升高，48h達(dá)到高峰，15d仍高于假手術(shù)組（P 0.05）；COX2蛋白表達(dá)2h開始升高，7d達(dá)到高峰，15d仍高于假手術(shù)組（P 0.01）；PGI2/TXA2的比值再灌注30min時(shí)開始升高，再灌注48h達(dá)到高峰后逐漸下降，15d時(shí)仍顯著高于假手術(shù)組（P 0.05）。與GCIR組比較，PDTC預(yù)處理組（在缺血前1小時(shí)分別給予100mg·kg-1和200mg·kg-1PDTC腹腔注射）第7至12天大鼠尋臺(tái)潛伏期明顯縮短；再灌注第12天神經(jīng)元核固縮減少，NF-κB蛋白、COX2mRNA及蛋白表達(dá)減少，PGI2/TXA2比值降低。 結(jié)論：NF-κB活化可能上調(diào)GCIR大鼠海馬神經(jīng)元中COX2表達(dá)水平，使PGI2/TXA2比值升高，進(jìn)而參與腦損傷病理生理過程的調(diào)節(jié)。PDTC對(duì)GCIR后大鼠神經(jīng)元損傷有長時(shí)程保護(hù)作用，其機(jī)制可能涉及抑制NF-κB，下調(diào)COX2表達(dá)，降低PGI2/TXA2比值。
[Abstract]:Aim: to investigate the protective effect of pyrrolidine dithiocarbamate (pyrrolidine dithiocarbamic, PDTC), an inhibitor of nuclear transcription factor 魏 B (nuclear factor- 魏 B (NF- 魏 B), on neuronal injury in rats with global cerebral ischemia-reperfusion (global cerebral ischemia reperfusion,GCIR). Methods: GCIR model was established by clipping bilateral common carotid artery (20min) with systemic hypotension. Morris water maze was used to detect spatial learning and memory ability. The number and morphology of hippocampal neurons in rats were observed by HE routine staining. RT-PCR was used to detect the mRNA expression of cyclooxygenase-2 (cyclooxygenase2, COX2) in hippocampus of rats. The expression of COX2 protein in hippocampus of NF- 魏 B was detected by immunohistochemistry. The levels of prostacyclin (prostacyclin,PGI2) and thromboxane A2 (thromboxaneA2,TXA2) in hippocampus of rats were determined by Elisa. Results: compared with the sham-operated group, the spatial learning and memory ability of (sham) rats decreased significantly, and the apoptosis of hippocampal neurons 30min began to appear (P0. 05) and reached the peak at 7 days (P0. 05). The expression of NF- 魏 B protein was significantly higher than that of sham operation group (P 0.01) at the beginning of 24 h and reaching the peak at 24 h and reaching the peak at 15 d (P0. 01). The expression of COX-2 mRNA in sham operation group was significantly higher than that in sham operation group (P 0. 05). The expression of COX2 protein increased at 2 h and reached the peak at day 7 and reached the peak at day 15. The ratio of PGI2 / TXA2 in sham-operated group was still higher than that in sham operation group (P0.01). The ratio of PGI2 / TXA2 in sham operation group was significantly higher than that in sham-operation group after 48 hours of reperfusion, and then gradually decreased at 48h after reperfusion (P0. 05). Compared with the GCIR group, the incubation period of the rats in the PDTC pretreatment group (intraperitoneal injection of 100mg kg-1 and 200mg kg-1PDTC at 1 hour before ischemia) was significantly shortened on the 7th to 12th day. On the 12th day after reperfusion, the expression of COX2 mRNA and protein of NF- 魏 B protein decreased and the ratio of PGI 2 / TXA2 decreased. Conclusion the activation of fraction NF- 魏 B may up-regulate the expression of COX2 in hippocampal neurons of GCIR rats, increase the ratio of PGI2/TXA2, and participate in the regulation of pathophysiological process of brain injury. PDTC has a long-term protective effect on neuronal injury after GCIR. The mechanism may involve inhibition of NF- 魏 B, down-regulation of COX2 expression and reduction of PGI2/TXA2 ratio.
【學(xué)位授予單位】：重慶醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2014
【分類號(hào)】：R965

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