浏览全部资源
扫码关注微信
1.天津医科大学总医院药剂科,天津 300052
2.天津医科大学基础医学院遗传学系,天津 300070
3.天津医科大学总医院消化科,天津 300052
主管药师,硕士。研究方向:消化系统疾病的临床药学。E-mail:xiedongsuper@163.com
主任医师,博士生导师,博士。研究方向:炎症性肠病和消化道免疫疾病的诊断和治疗。E-mail:doccaoxc@163.com
纸质出版日期:2024-07-15,
收稿日期:2024-03-26,
修回日期:2024-05-22,
扫 描 看 全 文
谢栋,刘媛媛,李正翔等.芒柄花素调节Hippo/YAP信号通路对炎症性肠病大鼠肠上皮细胞凋亡的影响 Δ[J].中国药房,2024,35(13):1564-1569.
XIE Dong,LIU Yuanyuan,LI Zhengxiang,et al.Effects of formononetin on the apoptosis of intestinal epithelial cells in rats with inflammatory bowel disease by regulating the Hippo/YAP signaling pathway[J].ZHONGGUO YAOFANG,2024,35(13):1564-1569.
谢栋,刘媛媛,李正翔等.芒柄花素调节Hippo/YAP信号通路对炎症性肠病大鼠肠上皮细胞凋亡的影响 Δ[J].中国药房,2024,35(13):1564-1569. DOI: 10.6039/j.issn.1001-0408.2024.13.04.
XIE Dong,LIU Yuanyuan,LI Zhengxiang,et al.Effects of formononetin on the apoptosis of intestinal epithelial cells in rats with inflammatory bowel disease by regulating the Hippo/YAP signaling pathway[J].ZHONGGUO YAOFANG,2024,35(13):1564-1569. DOI: 10.6039/j.issn.1001-0408.2024.13.04.
目的
2
探究芒柄花素(FMN)对炎症性肠病(IBD)大鼠肠上皮细胞凋亡的影响及可能机制。
方法
2
采用三硝基苯磺酸诱导的方法构建大鼠IBD模型。将造模成功的48只大鼠按照随机数字表法分为模型组(生理盐水),低、高剂量FMN组(20、40 mg/kg FMN)和高剂量FMN+YAP抑制剂Verteporfin(VTPF)组(40 mg/kg FMN+10 mg/kg VTPF),每组12只;另取12只大鼠设为正常组(生理盐水);每天给药/生理盐水1次,连续7 d。末次给药后,对大鼠疾病活动指数(DAI)进行评分;测量大鼠结肠长度;观察大鼠结肠组织的病理学变化;检测大鼠血清中肿瘤坏死因子α(TNF-α)、白细胞介素6(IL-6)、IL-10水平;检测大鼠肠上皮细胞的凋亡情况;检测大鼠结肠组织中Yes相关蛋白(YAP)、切割型胱天蛋白酶3(cleaved-caspase-3)、B细胞淋巴瘤2(Bcl-2)、Bcl-2相关X蛋白(Bax)表达。
结果
2
与正常组比较,模型组大鼠DAI评分,TNF-α、IL-6水平,肠上皮细胞凋亡率,cleaved-caspase-3、Bax蛋白表达水平均显著升高(
P
<0.05);结肠长度显著变短(
P
<0.05);IL-10水平和YAP、Bcl-2蛋白表达水平均显著降低(
P
<0.05);结肠组织出现细胞形态异常、排列紊乱,炎症细胞浸润等病理学变化。与IBD组比较,低剂量FMN组、高剂量FMN组大鼠上述指标水平均显著改善(
P
<0.05),且具有剂量依赖性(
P
<0.05);而加入VTPF后,显著逆转了FMN对IBD大鼠上述指标的改善作用(
P
<0.05)。
结论
2
FMN可能是通过抑制Hippo/YAP信号通路,促进YAP的表达,进而抑制IBD大鼠肠上皮细胞凋亡。
OBJECTIVE
2
To investigate the effects of formononetin (FMN) on the apoptosis of intestinal epithelial cells in inflammatory bowel disease (IBD) rats and its possible mechanism.
METHODS
2
IBD rat model was constructed by using trinitrobenzene sulfonic acid (TNBS) induction. Forty-eight rats with successful modeling were divided into model group (normal saline), low-dose and high-dose FMN groups (20 and 40 mg/kg FMN), and high-dose FMN+YAP inhibitor Verteporfin (VTPF) group (40 mg/kg FMN+10 mg/kg VTPF), with 12 rats in each group. Another 12 rats were set as the normal group (normal saline). They were given drug/normal saline, once a day, for 7 consecutive days. After the last administration, the disease activity index (DAI) of rats was calculated, and the colon length of rats in each group was measured. The pathological changes in the colon tissue of rats were observed. The levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and IL-10 in serum were detected, and the apoptosis of intestinal epithelial cells was detected. The expressions of Yes associated protein (YAP), cleaved cysteine-containing aspartate proteolytic enzyme 3 (cleaved-caspase-3), B-cell lymphoma-2 (Bcl-2) and Bcl-2 associated X protein (Bax) were detected in colon tissue of rats.
RESULTS
2
Compared with the normal group, DAI score, the levels of TNF-α and IL-6, the apoptotic rate of intestinal epithelial cells, and the expressions of cleaved-caspase-3 and Bax protein in the model group were increased greatly (
P
<0.05); the length of the colon was greatly decreased (
P
<0.05), and the serum level of IL-10 and the protein expressions of YAP and Bcl-2 were greatly reduced (
P
<0.05). The cell morphology of colon tissue was abnormal, with disordered arrangement and inflammatory cell infiltration. Compared with IBD group, the above indexes of rats were improved significantly in low-dose and high-dose FMN groups (
P
<0.05), in dose-dependent manner (
P
<0.05). VTPF significantly alleviated the effects of FMN on the above indexes of IBD rats (
P
<0.05).
CONCLUSIONS
2
FMN may promote the expression of YAP by inhibiting the Hippo/YAP signaling pathway, thereby inhibiting apoptosis of intestinal epithelial cells in IBD rats.
芒柄花素Hippo/YAP信号通路炎症性肠病肠上皮细胞细胞凋亡
Hippo/YAP signaling pathwayinflammatory bowel diseaseintestinal epithelial cellscell apoptosis
GILLILAND A,CHAN J J,DE WOLFE T J,et al. Pathobionts in inflammatory bowel disease:origins,underlying mechanisms,and implications for clinical care[J].Gastroenterology,2024,166(1):44-58.
BRUNER L P,WHITE A M,PROKSELL S. Inflammatory bowel disease[J]. Prim Care,2023,50(3):411-427.
ZHANG J,CEN L,ZHANG X F,et al. MPST deficiency promotes intestinal epithelial cell apoptosis and aggravates inflammatory bowel disease via AKT[J]. Redox Biol,2022,56:102469.
YU L,ZHANG Y Y,CHEN Q Q,et al. Formononetin protects against inflammation associated with cerebral ischemia-reperfusion injury in rats by targeting the JAK2/STAT3 signaling pathway[J]. Biomed Pharmacother,2022,149:112836.
李婷,邹秋萍,毛泽伟,等.三点金中黄酮类化合物对溃疡性结肠炎小鼠的干预作用及其对肠道菌群的影响[J].中国比较医学杂志,2022,32(4):29-38.
LI T,ZOU Q P,MAO Z W,et al. Therapeutic effect of flavonoids from Desmodium triflorum on an ulcerative colitis mouse model and the influence on intestinal flora[J]. Chin J Comp Med,2022,32(4):29-38.
尤雯丽,乔翠霞,张立,等.炎症性肠病中Hippo信号通路的研究进展[J].中华炎性肠病杂志,2020,6(2):150-153.
YOU W L,QIAO C X,ZHANG L,et al. Research pro- gress of Hippo signaling pathway in inflammatory bowel disease[J]. Chin J Inflamm Bowel Dis,2020,6(2):150-153.
吴茸,王栋,王晶敏,等.苦参碱调节IL-6/STAT3/NF-κB信号通路对炎症性肠病大鼠Th17/Treg平衡的影响[J]. 西安交通大学学报(医学版),2023,44(5):809-816.
WU R,WANG D,WANG J M,et al. Influence of matrine on Th17/Treg balance in rats with inflammatory bowel disease by regulating IL-6/STAT3/NF-κB signaling pathway[J]. J Xi’an Jiaotong Univ Med Sci,2023,44(5):809-816.
卢迎宏,王丹,井海云,等.芒柄花素对大鼠心肌缺血再灌注损伤的影响及其机制[J]. 中国老年学杂志,2023,43(5):1147-1151.
LU Y H,WANG D,JING H Y,et al. Effect of formononetin on myocardial ischemia-reperfusion injury in rats and its mechanism[J]. Chin J Gerontol,2023,43(5):1147-1151.
邓新超,钱亮,邹曼. 藏红花素调节Hippo-YAP信号通路抑制膝骨关节炎大鼠软骨细胞凋亡[J]. 中国骨质疏松杂志,2023,29(4):538-543,598.
DENG X C,QIAN L,ZOU M. Crocin regulates Hippo-YAP signal pathway and inhibits chondrocyte apoptosis in rats with knee osteoarthritis[J]. Chin J Osteoporos,2023,29(4):538-543,598.
JERGENS A E,PARVINROO S,KOPPER J,et al. Rules of engagement:epithelial-microbe interactions and inflammatory bowel disease[J]. Front Med,2021,8:669913.
HU K,YUAN X Z,HE H,et al. Pharmacological mechanisms of chitotriose as a redox regulator in the treatment of rat inflammatory bowel disease[J]. Biomed Pharmacother,2022,150:112988.
SILVA I,SOLAS J,PINTO R,et al. Chronic experimental model of TNBS-induced colitis to study inflammatory bowel disease[J]. Int J Mol Sci,2022,23(9):4739.
QIU J L,WU C X,GAO Q Y,et al. Effect of fecal microbiota transplantation on the TGF-β1/Smad signaling pathway in rats with TNBS-induced colitis[J]. Ann Transl Med,2022,10(15):825.
ENGEVIK M A,HERRMANN B,RUAN W,et al. Bifidobacterium dentium-derived γ-glutamylcysteine suppresses ER-mediated goblet cell stress and reduces TNBS-driven colonic inflammation[J]. Gut Microbes,2021,13(1):1-21.
WU D C,WU K Y,ZHU Q T,et al. Formononetin admi- nistration ameliorates dextran sulfate sodium-induced acute colitis by inhibiting NLRP3 inflammasome signa- ling pathway[J]. Mediators Inflamm,2018,2018:3048532.
YANG J,SHA X W,WU D,et al. Formononetin alle- viates acute pancreatitis by reducing oxidative stress and modulating intestinal barrier[J]. Chin Med,2023,18(1):78.
ZHOU W,LIM A,EDDERKAOUI M,et al. Role of YAP signaling in regulation of programmed cell death and drug resistance in cancer[J]. Int J Biol Sci,2024,20(1):15-28.
DENG F H,WU Z R,ZOU F,et al. The Hippo-YAP/TAZ signaling pathway in intestinal self-renewal and regeneration after injury[J]. Front Cell Dev Biol,2022,10:894737.
DENG F H,WU Z R,XU M M,et al. YAP activates STAT3 signaling to promote colonic epithelial cell prolife- ration in DSS-induced colitis and colitis associated cancer[J]. J Inflamm Res,2022,15:5471-5482.
YAN S G,WANG P,WEI H L,et al.Treatment of ulcera- tive colitis with Wumei wan by inhibiting intestinal inflammatory response and repairing damaged intestinal mucosa[J]. Phytomedicine,2022,105:154362.
0
浏览量
0
下载量
0
CSCD
关联资源
相关文章
相关作者
相关机构