[1]万咪咪,傅张倚天,何璐平,等.基于TREM2介导的炎症信号通路观察电针缓解2型糖尿病干眼大鼠眼表感觉异常的作用机制[J].眼科新进展,2024,44(4):258-263.[doi:10.13389/j.cnki.rao.2024.0051]
　WAN Mimi,FU Zhangyitian,HE Luping,et al.Observation of the mechanism of electroacupuncture in relieving ocular surface sensory abnormalities in rats with type 2 diabetes and dry eyes based on triggering receptor expressed on myeloid cells 2-mediated inflammatory signaling pathway[J].Recent Advances in Ophthalmology,2024,44(4):258-263.[doi:10.13389/j.cnki.rao.2024.0051]
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基于TREM2介导的炎症信号通路观察电针缓解2型糖尿病干眼大鼠眼表感觉异常的作用机制/HTML
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《眼科新进展》[ISSN:1003-5141/CN:41-1105/R]

卷:
44卷
期数:
2024年4期
页码:
258-263
栏目:
实验研究
出版日期:
2024-04-05

文章信息/Info

Title:
Observation of the mechanism of electroacupuncture in relieving ocular surface sensory abnormalities in rats with type 2 diabetes and dry eyes based on triggering receptor expressed on myeloid cells 2-mediated inflammatory signaling pathway
作者:
万咪咪; 傅张倚天; 何璐平; 孙心怡; 高卫萍
210024　江苏省南京市，南京中医药大学附属医院眼科（万咪咪，傅张倚天，何璐平，高卫萍）；210024　江苏省南京市，南京中医药大学附属医院内分泌科（孙心怡）
Author(s):
WAN Mimi1; FU Zhangyitian1; HE Luping1; SUN Xinyi2; GAO Weiping1
1.Department of Ophthalmology,Affiliated Hospital of Nanjing University of Traditional Chinese Medicine,Nanjing 210024,Jiangsu Province,China
2.Department of Endocrinology,Affiliated Hospital of Nanjing University of Traditional Chinese Medicine,Nanjing 210024,Jiangsu Province,China
关键词:
2型糖尿病; 干眼; 电针; 髓系细胞触发受体2; 炎症
Keywords:
type 2 diabetes;  dry eye;  electroacupuncture;  triggering receptor expressed on myeloid cells 2;  inflammation
分类号:
R777.34
DOI:
10.13389/j.cnki.rao.2024.0051
文献标志码:
A
摘要:
目的　揭示电针调控2型糖尿病干眼大鼠三叉神经节（TG）和三叉神经脊核尾状核（SpⅤc）中髓系细胞触发受体2（TREM2）介导的神经炎症信号通路缓解眼表感觉异常的潜在机制。
方法　健康雄性SD大鼠高糖高脂饮食4周后，腹腔注射10 g·L-1链脲佐菌素诱导建立2型糖尿病干眼大鼠模型。实验第12周造模成功的大鼠随机分为模型组、电针组、假针组、氟米龙组，并选择普通饲料喂养的健康雄性SD大鼠设为空白组，各组干预2周。造模前、造模后及干预后各组大鼠均行角膜荧光素钠染色（FL）、酚红棉线试验（PRT）、泪膜破裂时间（BUT）和角膜机械知觉（CTT）检查，观察各组大鼠TG和SpⅤc组织形态变化及TREM2阳性表达部位，检测在各组大鼠TG和SpⅤc中TREM2、白细胞介素-18（IL-18）和白细胞介素-1β（IL-1β）的mRNA表达。
结果　造模后，与空白组比较，其余各组大鼠FL评分显著升高，PRT、BUT、CTT显著降低，差异均有统计学意义（均为P<0.01）。干预后，与模型组比较，电针组、氟米龙组大鼠FL评分显著降低，PRT、BUT、CTT显著升高，差异均有统计学意义（均为P<0.01），假针组以上指标差异均无统计学意义（均为P>0.05)。与电针组比较，氟米龙组、假针组大鼠PRT、CTT显著降低，假针组大鼠FL评分显著升高、BUT显著降低，差异均有统计学意义（均为P<0.01），氟米龙组大鼠FL评分、BUT差异无统计学意义（均为P>0.05）。与假针组比较，氟米龙组大鼠FL评分降低，PRT、BUT、CTT升高，差异均有统计学意义（P<0.05）。免疫荧光双标染色结果显示，TREM2在模型组大鼠TG和SpⅤc中激活的小胶质细胞上阳性表达。TG和SpⅤc的RT-PCR检测结果显示，与空白组比较，模型组、电针组、氟米龙组、假针组TG和SpⅤc中TREM2 mRNA表达降低，模型组TG和SpⅤc及假针组TG中IL-18和IL-1β mRNA，以及假针组SpⅤc中IL-18 mRNA表达增加，差异均有统计学意义（均为P<0.05）。与模型组比较，电针组、氟米龙组TG和SpⅤc中TREM2 mRNA表达增加，IL-18和IL-1β mRNA表达降低，差异均有统计学意义（均为P<0.05）。与电针组比较，假针组TG和SpⅤc中TREM2 mRNA表达降低，IL-18和IL-1β mRNA表达增加，差异均有统计学意义（均为P<0.05），氟米龙组TG和SpⅤc中TREM2、IL-18及IL-1β mRNA表达差异均无统计学意义（均为P>0.05）。与假针组比较，氟米龙组TG、SpⅤc中TREM2 mRNA表达增加，SpⅤc中IL-18 mRNA表达降低，差异均有统计学意义（均为P<0.05），氟米龙组TG、SpⅤc中IL-1β mRNA及TG中IL-18 mRNA表达差异均无统计学意义（均为P>0.05）。
结论　电针通过调控TG和SpⅤc中TREM2介导的炎症信号通路，可有效缓解2型糖尿病干眼大鼠眼表感觉异常。
Abstract:
Objective　To reveal the potential mechanism of electroacupuncture regulating the neuroinflammatory signaling pathway mediated by triggering receptor expressed on myeloid cells 2 (TREM2) in trigeminal ganglion (TG) and caudate nucleus of spinal trigeminal nucleus (SpⅤc) of rats with type 2 diabetes and dry eyes and alleviating ocular surface sensory abnormalities.
Methods　Healthy male Sprague-Dawley (SD) rats were induced by intraperitoneal injection of 10 g·L-1 streptozotocin to establish a type 2 diabetes dry eye rat model after 4 weeks of high-glucose and high-fat diets. In the 12th week of the experiment, successfully modeled rats were randomly divided into the model group, electroacupuncture group, sham-acupuncture group and fluorometholone group, and healthy male SD rats fed with normal diets were selected as the blank group. Rats in all groups were intervened for 2 weeks. The corneal fluorescein sodium staining (FL), tear secretion ［detected by phenol red thread (PRT) test］, tear film break-up time (BUT), and corneal touch threshold (CTT) in each group were measured before, after modeling, and after the intervention. The changes in tissue morphology of TG and SpⅤc and TREM2 positive expression sites in each group were observed. The messenger ribonucleic acid (mRNA) expression of TREM2, interleukin-18 (IL-18) and interleukin-1β (IL-1β) of TG and SpⅤc in each group were detected.
Results　After modeling, compared with the blank group, the FL scores of rats significantly increased and PRT, BUT and CTT significantly decreased in other groups (all P<0.01). After the intervention, compared with the model group, the electroacupuncture group and fluorometholone group showed significant reductions in FL scores and significant increases in PRT, BUT and CTT (all P<0.01); there was no statistically significant difference in these indicators in the sham-acupuncture group (all P>0.05). Compared with the electroacupuncture group, the PRT and CTT of rats in the fluorometholone group and sham-acupuncture group were significantly reduced, the FL score significantly increased and BUT significantly decreased in the sham-acupuncture group (all P<0.01), and there was no statistically significant difference in FL score and BUT of rats in the fluorometholone group (both P>0.05). Compared with the sham-acupuncture group, the fluorometholone group showed a decrease in FL score and an increase in PRT, BUT and CTT in rats, with statistically different significances (all P<0.05). The immunofluorescence double-labeling assay showed a positive expression of TREM2 in activated microglia of TG and SpⅤc in the model group. The reverse transcription-polymerase chain reaction of TG and SpⅤc showed that compared with the blank group, the TREM2 mRNA expression in the TG and SpⅤc of the model group, electroacupuncture group, fluorometholone group and sham-acupuncture group decreased, the IL-18 and IL-1β mRNA in TG and SpⅤc of the model group, IL-18 and IL-1β mRNA in TG and IL-1β mRNA in SpⅤc of the sham-acupuncture group increased (all P<0.05); compared with the model group, the TREM2 mRNA expression increased and IL-18 and IL-1β mRNA expression decreased in the TG and SpⅤc of the electroacupuncture group and fluorometholone group (all P<0.05).
Conclusion　Electroacupuncture can effectively alleviate the ocular surface sensory abnormalities of rats with type 2 diabetes and dry eyes by regulating the inflammatory signaling pathway mediated by TREM2 in TG and SpⅤc.

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备注/Memo

备注/Memo:
国家自然科学基金项目（编号：82074526）；江苏省研究生科研与实践创新计划项目（编号：KYCX23_2138）
更新日期/Last Update: 2024-04-05