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姜黄素对视网膜缺血-再灌注损伤大鼠视网膜IL-1β表达的影响
引用本文:张宁,尹伊,徐莹,肖培伦,李晓双,王晓莉,赵岩松.姜黄素对视网膜缺血-再灌注损伤大鼠视网膜IL-1β表达的影响[J].眼科新进展,2023,0(3):178-184.
作者姓名:张宁  尹伊  徐莹  肖培伦  李晓双  王晓莉  赵岩松
作者单位:261041 山东省潍坊市,潍坊医学院附属医院眼科(张宁,尹伊,徐莹,赵岩松);261053 山东省潍坊市,潍坊医学院基础医学院(肖培伦,李晓双);261053 山东省潍坊市,潍坊医学院影像学院(王晓莉)
基金项目:山东省中医药科技发展计划项目(编号:2019-0417,2019-0421);;山东省自然科学基金(编号:ZR2021MH351,ZR2020MH074);;国家自然科学基金(编号:82071888);;潍坊市科学技术计划发展项目(编号:2021GX057,2021YX039);
摘    要:目的 观察姜黄素(CUR)对视网膜缺血-再灌注损伤(RIRI)大鼠视网膜白细胞介素-1β(IL-1β)表达的影响,从Toll样受体4/半胱氨酸天冬氨酸蛋白酶-8(TLR4/Caspase-8)通路探讨其机制,为CUR治疗RIRI的临床应用提供科学的理论依据。方法 SPF级健康无眼疾雄性SD大鼠102只,随机分为Sham组(n=10)、RIRI组(n=35)、RIRI+TLR4抑制剂(TAK-242)组(n=11)、RIRI+CUR组(n=35)及RIRI+CUR+TAK-242组(n=11),其中,Sham组、RIRI组及RIRI+CUR组根据建模后时间不同分为建模后6 h、12 h、24 h、72 h及7 d组。采用前房高眼压灌注法建立RIRI模型为RIRI组,Sham组不做特殊处理,RIRI+TAK-242组、RIRI+CUR组、RIRI+CUR+TAK-242组分别于建模前腹腔注射相应药物。免疫组织化学染色检测建模后各时间点各组大鼠视网膜中IL-1β+、TLR4+ Caspase-8+细胞数;建模后12 h, We...

关 键 词:视网膜缺血-再灌注  姜黄素  白细胞介素-1β  TLR4/Caspase-8通路  大鼠

Effect of curcumin on the expression of interleukin-1β in the retina of rats with retinal ischemia-reperfusion injury
ZHANG Ning,YIN Yi,XU Ying,XIAO Peilun,LI Xiaoshuang,WANG Xiaoli,ZHAO Yansong.Effect of curcumin on the expression of interleukin-1β in the retina of rats with retinal ischemia-reperfusion injury[J].Recent Advances in Ophthalmology,2023,0(3):178-184.
Authors:ZHANG Ning  YIN Yi  XU Ying  XIAO Peilun  LI Xiaoshuang  WANG Xiaoli  ZHAO Yansong
Affiliation:1.Department of Ophthalmology,the Affiliated Hospital of Weifang Medical University,Weifang 261031,Shangdong Provine,China2.School of Basic Medicine,Weifang Medical University,Weifang 261053,Shangdong Provine,China3.School of Medical Imaging,Weifang Medical University,Weifang 261053,Shangdong Provine,China
Abstract:Objective To observe the effect of curcumin (CUR) on retinal interleukin-1β (IL-1β) of retinal ischemia-reperfusion injury (RIRI) rats and its mechanism from the toll-like receptor 4/cysteine-containing aspartate-specific proteases-8 (TLR4/Caspase-8) signaling pathway, providing a scientific theoretical basis for the clinical application of CUR in the treatment of RIRI.
Methods Totally 102 specific-pathogen-free healthy male Sprague Dawley rats without eye disease were included and randomly divided into the Sham group (n=10), RIRI group (n=35), RIRI+TLR4 inhibitor (TAK-242) group (n=11), RIRI+CUR group (n=35) and RIRI+CUR+TAK-242 group (n=11). Rats in the Sham Group, RIRI group and the RIRI+CUR group were further divided into subgroups according to the different time points after modeling: 6 h, 12 h, 24 h, 72 h and 7 d. The RIRI model was established by the anterior chamber ocular hypertension method in the RIRI group. Rats in the Sham group did not receive special treatment. Rats in the RIRI+TAK-242 group, the RIRI+CUR group and the RIRI+CUR+TAK-242 group were injected with corresponding drugs before modeling. The cell numbers of IL-1β+, TLR4+ and Caspase-8+ in the retinas of rats in each group at each time point after modeling were detected through immunohistochemical staining. The expression of TLR4, Caspase-8 and IL-1β in the retinas of rats in each group was detected via Western blot 12 h after modeling. The morphological changes of the retina of rats in each group were observed by hematoxylin-eosin staining.
Results The results of immunohistochemical staining showed that at 6 h, 12 h, 24 h, 72 h and 7 d after modeling, the cell number of IL-1β+ and TLR4+ significantly increased in the RIRI+CUR group compared with the Sham group. The cell number of IL-1β+ and TLR4+ significantly decreased in the RIRI+CUR group at each time point compared with the RIRI group. The cell number of IL-1β+ and TLR4+ significantly increased in the RIRI group at each time point compared with the Sham group. The above differences were statistically significant (all P<0.05). At 12 h after modeling, compared with the Sham group, the cell number of IL-1β+, TLR4+ and Caspase-8+, as well as the proteins IL-1β, TLR4 and Caspase-8 significantly increased in the RIRI group, RIRI+TAK-242 group, RIRI+CUR group and RIRI+CUR+TAK-242 group. The cell number of IL-1β+, TLR4+ and Caspase-8+, as well as the proteins IL-1β, TLR4 and Caspase-8 significantly decreased in the RIRI+TAK-242 group, RIRI+CUR group and RIRI+CUR+TAK-242 group compared with the RIRI group. The cell number of IL-1β+, TLR4+ and Caspase-8+, as well as the proteins IL-1β, TLR4 and Caspase-8 significantly increased in the RIRI+TAK-242 group and RIRI+CUR group compared with the RIRI+CUR+TAK-242 group. The above differences were statistically significant (all P<0.05). At 12 h after modeling, there was no statistically significant difference between the RIRI+TAK-242 group and the RIRI+CUR group in terms of the cell number of IL-1β+, TLR4+ and Caspase-8+ as well as the proteins IL-1β, TLR4 and Caspase-8 (all P>0.05). At 12 h after modeling, compared with the Sham group, the retinal inner layer cells in rats were edematous, the inner retinal layer was thickened, and the number of retinal ganglion cells (RGCs) was significantly reduced in the RIRI group, RIRI+TAK-242 group, RIRI+CUR group and RIRI+CUR+TAK-242 group.
Conclusion CUR can down-regulate the expression of IL-1β in the retina of RIRI rats, thereby reducing RIRI in rats. This mechanism may be related to the regulation of the TLR4/Caspase-8 signaling pathway by CUR, which has a neuroprotective effect.
Keywords:retinal ischemia-reperfusion  curcumin  interleukin-1β  toll-like receptor 4/cysteine-containing aspartate-specific proteases-8 signaling pathway  rats
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