出 处:《中国临床药理学杂志》2023年第11期1562-1566,共5页The Chinese Journal of Clinical Pharmacology
基 金:北京市自然科学基金资助项目(7202112)。
摘 要:目的探讨酪蛋白糖巨肽(CGMP)对老年消化性溃疡大鼠肠黏膜保护作用及机制。方法将50只Wistar大鼠分为对照组、模型组、CGMP低剂量组、CGMP高剂量组及阳性药组。除对照组外,其余组复制十二指肠溃疡模型,第4天开始干预,CGMP低剂量组、CGMP高剂量组分别灌胃给予50和500 mg·kg^(-1)的CGMP,阳性药组灌胃给予40 mg·kg^(-1)柳氮磺胺吡啶,对照组和模型组均灌胃给予等量0.9%NaCl,每天1次,连续7 d。比较各组十二指肠溃疡评分、细胞凋亡率及p65核因子-κB(NF-κB p65)、B细胞淋巴瘤2相关X蛋白(Bax)、胱天蛋白酶3(caspase-3)蛋白的表达水平。结果对照组、模型组、阳性药组和CGMP低、高剂量组的十二指肠溃疡评分分别为(0.23±0.10)、(3.16±0.14)、(1.40±0.24)、(2.50±0.18)和(1.64±0.22)分,细胞凋亡率分别为(6.73±1.88)%、(76.00±8.85)%、(36.81±9.61)%、(58.13±6.93)%和(49.93±7.96)%,NF-κB p65蛋白相对表达水平分别为0.28±0.02、1.12±0.08、0.49±0.07、0.96±0.06和0.80±0.04,Bax蛋白相对表达水平分别为0.12±0.03、0.99±0.04、0.39±0.06、0.87±0.69和0.51±0.05,caspase-3蛋白相对表达水平分别为0.11±0.03、0.94±0.05、0.22±0.05、0.75±0.07和0.39±0.06。模型组的上述指标与阳性药组和CGMP低、高剂量组比较,差异均有统计意义(均P<0.05);CGMP低、高剂量组的上述指标比较,差异均有统计学意义(均P<0.05)。结论CGMP对十二指肠消化性溃疡大鼠肠黏膜均有保护作用,其调控机制可能与NF-κB信号通路有关。Objective To investigate the protective effect and mechanism of casein glycomacropeptide(CGMP)on the intestinal mucosa of aged rats with peptic ulcer.Methods Fifty Wistar rats were divided into control group,model group,CGMP low-dose group,CGMP high-dose group and positive drug group.Except for the control group,the remaining groups replicated the duodenal ulcer model and started intervention on the 4th day.The CGMP low-dose group and CGMP high-dose group were given 50 and 500 mg·kg^(-1) CGMP,respectively,and the positive drug group was given sulfasalazine 40 mg·kg^(-1) intragastrically,the control group and the model group were given the same amount of normal saline once a day for 7 consecutive days.The duodenal ulcer score,cell apoptosis rate,p65 nuclear factor-κB(NF-κB p65),B-cell lymphoma 2 associated X protein(Bax),cysteine aspartic and specific protease 3(caspase-3)protein expression levels in each group were compared.Results In control group,model group,positive drug group and CGMP low-dose group,CGMP high-dose group,the duodenal ulcer scores were(0.23±0.10),(3.16±0.14),(1.40±0.24),(2.50±0.18)and(1.64±0.22)points;the apoptosis rates were(6.73±1.88)%,(76.00±8.85)%,(36.81±9.61)%,(58.13±6.93)%and(49.93±7.96)%;the expressions of NF-κB p65 were 0.28±0.02,1.12±0.08,0.49±0.07,0.96±0.06 and 0.80±0.04;the Bax expression were 0.12±0.03,0.99±0.04,0.39±0.06,0.87±0.69 and 0.51±0.05;the caspase-3 expression were 0.11±0.03,0.94±0.05,0.22±0.05,0.75±0.07 and 0.39±0.06,respectively.The above indexes in model group were statistically different compared with those in positive drug group and CGMP low-dose,high-dose groups(all P<0.05);there were statistically significant differences in the above indexes between CGMP low-dose and CGMP high-dose groups(all P<0.05).Conclusion CGMP has a protective effect on the intestinal mucosa of rats with duodenal peptic ulcer,and its regulatory mechanism may be related to the NF-κB signaling pathway.
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