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
Crocin regulates Hippo YAP signal pathway and inhibits chondrocyte apoptosis in rats with knee osteoarthritis
  
DOI:10.3969/j.issn.1006.7108.2023.04.014
中文关键词:  藏红花素  膝骨性关节炎  凋亡  Hippo/Yes信号通路
英文关键词:crocin  knee osteoarthritis  apoptosis  Hippo/Yes signaling pathway
基金项目:武汉市卫生和计划生育委员会科研项目(WZ17Q11)
作者单位
邓新超1 钱亮1* 邹曼2 1.武汉市第八医院骨科湖北 武汉 430010 2.满春街社区卫生服务中心湖北 武汉 430030 
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中文摘要:
      目的 探讨藏红花素(crocin)调节Hippo/Yes相关蛋白(YAP)信号通路对膝骨关节炎(KOA)大鼠软骨细胞凋亡的影响。方法 SD大鼠分为CK组、Model组、低剂量crocin组(crocin-L组,10 mg/kg)、高剂量crocin组(crocin-H组,40 mg/kg)、塞来昔布组(CLCX组,10 mg/kg)、crocin-H+VTPF(YAP抑制剂)组(40 mg/kg+10 mg/kg),每组12只。观察并记录大鼠热痛阈值、压痛阈值的变化;ELISA法检测大鼠血清中基质金属蛋白酶 (MMP)-3、MMP-13、白细胞介素(IL)-1β、IL-6水平;HE染色检测大鼠软骨组织病理变化并进行Mankin评分;TUNEL染色检测大鼠软骨细胞凋亡;免疫组化、Western blot检测Bcl2相关X蛋白(Bax)、天冬氨酸特异性半胱氨酸蛋白酶-3(Caspase-3)、p-YAP、YAP蛋白表达。结果 与CK组比较,Model组大鼠热痛阈值、压痛阈值、p-YAP蛋白表达降低,软骨组织病理损伤严重,MMP-3、MMP-13、IL-1β、IL-6水平、Mankin评分、软骨细胞凋亡率、Bax、Caspase-3、YAP蛋白表达升高(P<0.05);与Model组比较,crocin-L组、crocin-H组、CLCX组对应指标变化趋势与上述相反(P< 0.05);VTPF减弱了高剂量crocin对KOA大鼠软骨细胞凋亡的抑制作用。结论 crocin可能通过激活Hippo/YAP信号通路抑制KOA大鼠软骨细胞凋亡。
英文摘要:
      Objective To investigate the impact of crocin on the apoptosis of chondrocytes in rats with knee osteoarthritis (KOA) by regulating Hippo/Yes-associated protein (YAP) signaling pathway. Methods SD rats were separated into CK group, Model group, low-dose crocin group (crocin-L group, 10 mg/kg), high-dose crocin group (crocin-H group, 40 mg/kg), celecoxib group (CLCX group, 10 mg/kg), crocin-H+VTPF (YAP inhibitor) group (40 mg/kg+10 mg/kg), 12 in each group. the changes in thermal pain threshold and tenderness threshold of rats were observed and recorded; ELISA detect the levels of matrix metalloproteinase (MMP)-3, MMP-13, interleukin (IL)-1β, and IL-6 in rat serum; HE staining detect the pathological changes of rat cartilage tissue and Mankin score was performed; TUNEL staining detect apoptosis of rat chondrocytes; the expression of Bcl2 related X protein (Bax), aspartate specific cysteine proteinase-3 (Caspase-3), p-YAP and YAP protein were detected by immunohistochemistry and Western blot. Results Compared with CK group, the thermal pain threshold, tenderness threshold and p-YAP protein expression were decreased, and the cartilage tissue was severely damaged, the MMP-3, MMP-13, IL-1β, IL-6 levels, Mankin score, chondrocyte apoptosis rate, Bax, Caspase-3, YAP protein expressions increased in the Model group (P<0.05); compared with Model group, the corresponding indicators in the crocin-L group, crocin-H group and CLCX group had the opposite trends (P<0.05); VTPF attenuated the inhibitory effect of high-dose crocin on chondrocyte apoptosis in KOA rats. Conclusion Crocin may inhibit the apoptosis of chondrocytes in KOA rats by activating the Hippo/YAP signaling pathway.
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