CAJ | 학술논문

目的评价钙/钙调素依赖性蛋白激酶Ⅱ(CaMKⅡ)在慢性痛致大鼠认知功能障碍中的作用.方法实验Ⅰ 清洁级健康雄性SD大鼠24只,体重180～ 220 g,采用随机数字表法分为4组(n=6):假手术组(S组)、假手术前注射m-AIP组(M-S组)、坐骨神经慢性压迫性损伤组(N-C组)和坐骨神经慢性压迫性损伤(CCI)术前注射m-AIP组(M-C组).S组及M-S组仅暴露坐骨神经但不进行结扎,其余各组采用CCI法制备慢性痛模型.S组及M-S组分别于假手术前15 min鞘内注射生理盐水20 μl及m-AIP 20μl;N-C组及M-C组分别于CCI术前15 min鞘内注射生理盐水20μl及m-AIP 20μl.于术前及术后第4、7、10、14、17、21和28天时测定大鼠热缩足潜伏期(TWL)及机械缩足反应阈(MWT),于术前及术后第7、14、21和28天时测定步入潜伏期时间(STL).实验Ⅱ 清洁级健康雄性SD大鼠18只,体重180～ 220 g,采用随机数字表法分为3组(n=6):假手术后注射m-AIP组(S-M组)、CCI术后对照组(C-N组)、CCI术后注射m-AIP组(C-M组).S-M组假手术后7d鞘内注射m-AIP 20μl,C-N组及C-M组于CCI分别于术后7d鞘内注射生理盐水20 μl及m-AIP 20μl.于给药前及给药后2、4和8h时测定TWL、MWT和STL.结果实验Ⅰ 与S组比较,N-C组术后各时点TWL缩短,MWT降低,术后第7、14和21天时STL缩短,M-C组术后各时点TWL缩短,MWT降低,术后第14和21天时STL缩短(P＜0.05);与N-C组比较,M-C组术后第4、7和10天时MWT升高,第4和7天时TWL延长,第7天时STL延长(P＜0.05).实验Ⅱ 与S-M组比较,C-N组给药后各时点TWL和STL缩短,MWT降低,C-M组给药后各时点STL缩短,给药后8h时TWL缩短,MWT降低(P＜0.05),给药后2和4h时TWL和MWT差异无统计学意义(P＞0.05).与C-N组比较,C-M组给药后2和4h时TWL延长,MWT升高(P＜0.05),各时点STL差异无统计学意义(P＞0.05).结论 CaMKⅡ参与了慢性痛致大鼠认知功能障碍的形成.
목적 평개개/개조소의뢰성단백격매Ⅱ(CaMKⅡ)재만성통치대서인지공능장애중적작용.방법 실험Ⅰ 청길급건강웅성SD대서24지,체중180～ 220 g,채용수궤수자표법분위4조(n=6):가수술조(S조)、가수술전주사m-AIP조(M-S조)、좌골신경만성압박성손상조(N-C조)화좌골신경만성압박성손상(CCI)술전주사m-AIP조(M-C조).S조급M-S조부폭로좌골신경단불진행결찰,기여각조채용CCI법제비만성통모형.S조급M-S조분별우가수술전15 min초내주사생리염수20 μl급m-AIP 20μl;N-C조급M-C조분별우CCI술전15 min초내주사생리염수20μl급m-AIP 20μl.우술전급술후제4、7、10、14、17、21화28천시측정대서열축족잠복기(TWL)급궤계축족반응역(MWT),우술전급술후제7、14、21화28천시측정보입잠복기시간(STL).실험Ⅱ 청길급건강웅성SD대서18지,체중180～ 220 g,채용수궤수자표법분위3조(n=6):가수술후주사m-AIP조(S-M조)、CCI술후대조조(C-N조)、CCI술후주사m-AIP조(C-M조).S-M조가수술후7d초내주사m-AIP 20μl,C-N조급C-M조우CCI분별우술후7d초내주사생리염수20 μl급m-AIP 20μl.우급약전급급약후2、4화8h시측정TWL、MWT화STL.결과 실험Ⅰ 여S조비교,N-C조술후각시점TWL축단,MWT강저,술후제7、14화21천시STL축단,M-C조술후각시점TWL축단,MWT강저,술후제14화21천시STL축단(P＜0.05);여N-C조비교,M-C조술후제4、7화10천시MWT승고,제4화7천시TWL연장,제7천시STL연장(P＜0.05).실험Ⅱ 여S-M조비교,C-N조급약후각시점TWL화STL축단,MWT강저,C-M조급약후각시점STL축단,급약후8h시TWL축단,MWT강저(P＜0.05),급약후2화4h시TWL화MWT차이무통계학의의(P＞0.05).여C-N조비교,C-M조급약후2화4h시TWL연장,MWT승고(P＜0.05),각시점STL차이무통계학의의(P＞0.05).결론 CaMKⅡ삼여료만성통치대서인지공능장애적형성.
Objective To evaluate the role of calcium/calmodulin-dependent protein kinase Ⅱ (CaMK Ⅱ) in cognitive dysfunction caused by chronic pain in rats.Methods The experiment was performed in 2 parts.In experiment Ⅰ,24 pathogen-free male Sprague-Dawley rats,weighing 180-220 g,were randomly divided into 4 groups (n =6 each) using a random number table:sham operation group (group S),m-AIP injected before sham operation group (group M-S),chronic sciatic nerve injury group (group N-C),and m-AIP injected before chronic constriction injury (CCI) group (group M-C).The sciatic nerve was only exposed but not ligated.Chronic pain was induced by CCI in N-C and M-C groups.The animals were anesthetized with intraperitoneal 1％ pentobarbital sodium.The sciatic nerve was exposed and 4 ligatures were placed on the sciatic nerve at 1 mm intervals.Normal saline 20 μ1 and m-AIP 20 μ/ were injected intrathecally at 15 min before sham operation in S and M-S groups,respectively,and at 15 min before CCI in N-C and M-C groups,respectively.The mechanical paw withdrawal threshold (MWT) and thermal paw withdrawal latency (TWL) were measured before CCI and on 4,7,10,14,17,21 and 28 days after CCI.Step-through latency (STL) was measured before CCI and on 7,14,21 and 28 days after CCI.In experiment Ⅱ,18 pathogen-free male Sprague-Dawley rats,weighing 180-220 g,were randomly divided into 3 groups (n =6 each) using a random number table:m-AIP injected after sham operation group (group C-N),control after CCI group (group C-N) and m-AIP injected after CCI group (group C-M).Group S-M received intrathecal injection of m-AIP 20 μl at 7 days after sham operation.Normal saline 20 μl and m-AIP 20 μ/ were injected intrathecally at 7 days after CCI in C-N and C-M groups,respectively.MWT,TWL and STL were measured before administration and at 2,4 and 8 h after administration.Results In experiment Ⅰ,compared with group S,MWT was significantly decreased at each time point after CCI,TWL was shortened at each time point after CCI and STL was shortened on 7,14 and 21 days after CCI in N-C group,and MWT was significandy decreased at each time point,TWL was shortened at each time point,and STL was shortened on 14 and 21 days after CCI in group M-C.Compared with group N-C,MWT was significantly increased on 4,7 and 10 days after CCI,TWL was prolonged on 4 and 7 days after CCI,and STL was prolonged on 7 days after CCI in group M-C.In experiment Ⅱ,compared with group S-M,MWT was significantly decreased,and TWL and STL were shortened at each time point after administration in C-N group,and TWL at 8 h after administration and STL at each time point after administration were shortened,MWT was decreased at 8 h after administration,and no significant change was found in MWT and TWL at 2 and 4 h after administration in group C-M Compared with group C-N,MWT was significantly increased,and TWL was prolonged at 2 and 4 h after administration,and no significant change was found in STL at each time point after administration in group C-M.Conclusion CaMK Ⅱ is involved in the development of cognitive dysfunction caused by chronic pain in rats.