CAJ | 학술논문

目的：探讨乌司他丁预先给药对大鼠海马CA1区缺血-再灌注损伤的影响及机制。方法采用雄性SD大鼠90只，采用随机数字法分为3组：假手术组（S组）、缺血-再灌注组（I/R组）和乌司他丁预处理组（U组），每组各30只。上述3个实验组按再灌注时间又分为再灌注2h、6h、1d、3d、7d五个亚组，每个亚组各6只。采用四动脉结扎法制备全脑缺血-再灌注模型，以原位缺口末端标记（TUNEL）法行海马CA1区的凋亡细胞检测，酶联免疫吸附法测定血清几丁质酶-3样蛋白-1（YKL-40）浓度，免疫组化法分析磷酸化c-Jun氨基末端激酶（p-JNK），并监测细胞外调节蛋白激酶（p-ERK）在海马CA1区的动态变化。结果三组大鼠间再灌注后各时间点血清YKL-40浓度、海马CA1区的凋亡细胞数目、p-JNK及p-ERK表达的比较，差异均有统计学意义（P均<0.05）。进一步两两比较，与S组比较，I /R组各时间点血清YKL-40浓度升高，海马CA1区的凋亡细胞数目、p-JNK及p-ERK的表达均明显增加（P均<0.05）；与I / R组比较，U组各时间点血清YKL-40浓度及p-ERK的表达显著升高，海马CA1区的凋亡细胞数目、p-JNK的表达均明显减少（P均<0.05）。结论乌司他丁预先给药可以减轻大鼠海马缺血-再灌注损伤，其机制可能与增加YKL-40的血清浓度，上调p-ERK和下调p-JNK的表达，减少神经元凋亡有关。
목적：탐토오사타정예선급약대대서해마CA1구결혈-재관주손상적영향급궤제。방법채용웅성SD대서90지，채용수궤수자법분위3조：가수술조（S조）、결혈-재관주조（I/R조）화오사타정예처리조（U조），매조각30지。상술3개실험조안재관주시간우분위재관주2h、6h、1d、3d、7d오개아조，매개아조각6지。채용사동맥결찰법제비전뇌결혈-재관주모형，이원위결구말단표기（TUNEL）법행해마CA1구적조망세포검측，매련면역흡부법측정혈청궤정질매-3양단백-1（YKL-40）농도，면역조화법분석린산화c-Jun안기말단격매（p-JNK），병감측세포외조절단백격매（p-ERK）재해마CA1구적동태변화。결과삼조대서간재관주후각시간점혈청YKL-40농도、해마CA1구적조망세포수목、p-JNK급p-ERK표체적비교，차이균유통계학의의（P균<0.05）。진일보량량비교，여S조비교，I /R조각시간점혈청YKL-40농도승고，해마CA1구적조망세포수목、p-JNK급p-ERK적표체균명현증가（P균<0.05）；여I / R조비교，U조각시간점혈청YKL-40농도급p-ERK적표체현저승고，해마CA1구적조망세포수목、p-JNK적표체균명현감소（P균<0.05）。결론오사타정예선급약가이감경대서해마결혈-재관주손상，기궤제가능여증가YKL-40적혈청농도，상조p-ERK화하조p-JNK적표체，감소신경원조망유관。
Objective To investigate the effect of ulinastatin pretreatment on hippocampal CA1 region with ischemia-reperfusion (I/R) injury in rats and its mechanism. Methods A total of 90 male SD rats were randomly divided into the sham operation group (group S), group I/R and ulinastatin pretreatment group (group U), 30 rats in each group. The three groups were further divided into the reperfusion 2 h, 6 h, 1 d, 3 d and 7 d subgroups, 6 rats in each subgroup. Global cerebral I / R model was established by 4-VO method. The TdT-mediated dUTP nick end labeling (TUNEL) method was used to detect the neuron apoptosis in hippocampal CA1 region. The enzyme linked immunosorbent (ELISA) method was used to measure the serum concentrations of YKL-40, and the immunohistochemical method was applied to investigate expression of phosphorylated c-Jun N-terminal kinase (p-JNK) and phosphorylated extracellular-regulated protein kinase (p-ERK) in hippocampal CA1 region. Results The serum concentrations of YKL-40, the number of apoptotic cells and expression of p-JNK and p-ERK after reperfusion at each time point all showed significant differences among the three group (all P<0.05). Compared with group S, the serum concentrations of YKL-40, the number of apoptot ic cells and expression of p-JNK and p-ERK were significantly increased at each time point after reperfusion in group I/R (all P<0.05). Compared with group I/R, the serum concentrations of YKL-40 and expression of p-JNK were higher, while the number of apoptotic cells and the expression of p-ERK was lower at each time point after reperfusion in group U as compared with group I/R (all P<0.05). Conclusion Ulinastatin pretreatment can reduce I/R injury in rats hippocampus CA1 region, which may be associated with the increased serum concentrations of YKL-40, up-regulation of p-ERK expression, down-regulation of p-JNK expression and neuronal apoptosis.