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慢性坐骨神經(jīng)損傷大鼠中腦導(dǎo)水管周圍灰質(zhì)MC4R的表達(dá)及HS014對(duì)熱痛覺(jué)過(guò)敏的影響

發(fā)布時(shí)間:2018-06-02 00:24

  本文選題:慢性坐骨神經(jīng)損傷 + 中腦導(dǎo)水管周圍灰質(zhì); 參考:《現(xiàn)代中西醫(yī)結(jié)合雜志》2016年35期


【摘要】:目的觀察大鼠慢性坐骨神經(jīng)損傷(CCI)后不同時(shí)間點(diǎn)中腦導(dǎo)水管周圍灰質(zhì)(PAG)4型黑皮質(zhì)素受體(MC4R)mRNA表達(dá)變化及給予選擇性MC4R拮抗劑HS014對(duì)CCI大鼠疼痛行為學(xué)的影響。方法 1將42只健康成年雄性Wistar大鼠隨機(jī)分為對(duì)照組6只、假手術(shù)組18只和CCI組18只,檢測(cè)各組大鼠術(shù)前和術(shù)后3,7,14 d熱縮足潛伏期(TWL),假手術(shù)組和CCI組分別于術(shù)后3,7,14 d,對(duì)照組于術(shù)后14 d TWL檢測(cè)完成后處死大鼠,取PAG腦組織,用半定量RT-PCR法檢測(cè)PAG腦區(qū)MC4R mRNA表達(dá)情況。2將30只健康成年雄性Wistar大鼠隨機(jī)分為對(duì)照組6只、假手術(shù)組6只和CCI組18只,均先進(jìn)行PAG置管。置管后7 d,CCI組隨機(jī)分成CCI+NS組、CCI+HS014 5μg組和CCI+HS014 10μg組,每組6只。假手術(shù)組和CCI各組手術(shù)造模。術(shù)后7 d,CCI+NS組經(jīng)導(dǎo)管注射生理鹽水0.5μL,CCI+HS014 5μg組注射HS014 5μg/0.5μL,CCI+HS014 10μg組注射HS014 10μg/0.5μL。檢測(cè)各組大鼠置管后7 d、術(shù)后7 d和干預(yù)后(注射后10~30 min完成檢測(cè))TWL。結(jié)果 CCI組大鼠術(shù)后3 d開(kāi)始出現(xiàn)TWL縮短(P0.05),術(shù)后7 d和14 d TWL縮短更加明顯(P均0.05),與對(duì)照組和假手術(shù)組比較差異均有統(tǒng)計(jì)學(xué)意義(P均0.05)。CCI組術(shù)后各時(shí)間點(diǎn)MC4RmRNA表達(dá)量均明顯高于對(duì)照組和假手術(shù)組(P均0.05),并且隨著CCI術(shù)后時(shí)間的推移,MC4RmRNA的表達(dá)量逐漸增高(P均0.05)。CCI各組大鼠術(shù)后7 d TWL明顯低于置管后7 d(P均0.05);CCI+NS組干預(yù)后TWL與術(shù)后7 d比較差異無(wú)統(tǒng)計(jì)學(xué)意義(P0.05),而CCI+HS014 5μg組和CCI+HS014 10μg組干預(yù)后TWL均明顯長(zhǎng)于術(shù)后7 d和CCI+NS組(P均0.05),CCI+HS014 10μg組干預(yù)后TWL明顯長(zhǎng)于CCI+HS014 5μg組(P0.05)。結(jié)論 CCI可引起PAG中MC4RmRNA的表達(dá)增加,其選擇性拮抗劑HS014可劑量依賴性減輕CCI大鼠的熱痛覺(jué)過(guò)敏,提示PAG中MC4R的表達(dá)增加可能參與神經(jīng)病理性疼痛的形成和維持。
[Abstract]:Objective to observe the changes of MC4RN mRNA expression in periaqueductal gray matter of rats with chronic sciatic nerve injury (CCI) at different time points and the effect of selective MC4R antagonist HS014 on the pain behavior of CCI rats. Methods 1 Forty-two healthy adult male Wistar rats were randomly divided into control group (n = 6), sham operation group (n = 18) and CCI group (n = 18). Rats in each group were examined for the latent period of thermal contraction of foot at 714 days before and 3 days after operation. The rats in sham operation group and CCI group were killed on the 14th day after operation, and the rats in the control group were killed after TWL detection on the 14th day after operation. The brain tissues of PAG were taken out. The expression of MC4R mRNA in PAG brain was detected by semi-quantitative RT-PCR. 2 30 healthy adult male Wistar rats were randomly divided into control group (n = 6), sham operation group (n = 6) and CCI group (n = 18). Seven days after catheterization, CCI group was randomly divided into CCI NS group (CCI 5 渭 g) and CCI HS014 10 渭 g group (6 rats in each group). Sham operation group and CCI group were operated to model. 7 days after operation, normal saline 0.5 渭 L and HS014 5 渭 g / 0.5 渭 L HS014 5 渭 g / 0.5 渭 L CCI HS014 10 渭 g / 10 渭 g / HS014 were injected into CCI NS group 7 days after operation. TWL was detected 7 days after catheterization, 7 days after operation and after intervention (1030 min after injection). Results in the CCI group, TWL shortening began to appear 3 days after operation (P 0.05), and TWL shortening on the 7th and 14th days after operation was more obvious (P 0.05). There was significant difference between the control group and the sham operation group in the expression of MC4RmRNA at different time points in the 0.05).CCI group. The expression of MC4R mRNA in 0.05).CCI group was significantly higher than that in control group and sham operation group (P 0.05). The expression of MC4R mRNA in 0.05).CCI group was significantly lower than that in control group and sham operation group on the 7th day after operation. The TWL was significantly lower in 0.05).CCI group than that in control group and sham operation group at 7 days after intervention and 7 days after operation. The expression of MC4R mRNA in 0.05).CCI group was significantly lower than that in control group and sham operation group. There was no significant difference in TWL between CCI HS014 5 渭 g group and CCI HS014 10 渭 g group (P 0.05), but the TWL of CCI HS014 5 渭 g group and CCI HS014 10 渭 g group was significantly longer than that of CCI HS014 5 渭 g group and CCI NS group (P 0.05). Conclusion CCI can increase the expression of MC4RmRNA in PAG, and its selective antagonist HS014 can attenuate the hyperthermia in CCI rats in a dose-dependent manner, suggesting that the increased expression of MC4R in PAG may be involved in the formation and maintenance of neuropathic pain.
【作者單位】: 內(nèi)蒙古醫(yī)科大學(xué)附屬醫(yī)院;青島大學(xué)醫(yī)學(xué)院附屬醫(yī)院;
【分類號(hào)】:R745.4

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