1.湘潭市中心医院药学部,湖南 湘潭 411100
2.湘潭市中心医院临床药学科,湖南 湘潭 411100
3.湘潭市中心医院中医科,湖南 湘潭 411100
Received:20 June 2025,
Published:25 December 2025
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张嘉妮,李文璨,李伟等.隐丹参酮改善糖尿病视网膜病变的机制研究[J].局解手术学杂志,2025,34(12):1051-1056.
ZHANG Jia-ni,LI Wen-can,LI Wei,et al.Mechanism of cryptotanshinone in improving diabetic retinopathy[J].JOURNAL OF REGIONAL ANATOMY AND OPERATIVE SURGERY,2025,34(12):1051-1056.
张嘉妮,李文璨,李伟等.隐丹参酮改善糖尿病视网膜病变的机制研究[J].局解手术学杂志,2025,34(12):1051-1056. DOI: 10.11659/jjssx.06E025100.
ZHANG Jia-ni,LI Wen-can,LI Wei,et al.Mechanism of cryptotanshinone in improving diabetic retinopathy[J].JOURNAL OF REGIONAL ANATOMY AND OPERATIVE SURGERY,2025,34(12):1051-1056. DOI: 10.11659/jjssx.06E025100.
目的
2
探究隐丹参酮(CTS)调控糖尿病视网膜病变(DR)的作用及潜在分子机制。
方法
2
将50只大鼠随机分为正常对照组(生理盐水处理)、糖尿病组(腹腔注射55 mg/kg链脲佐菌素建立糖尿病模型)、模型+H-CTS组(建模后给予75 μg的CTS处理)、模型+M-CTS组(建模后给予50 μg的CTS处理)和模型+L-CTS组(建模后给予25 μg的CTS处理)。采用10 ng/mL的肿瘤坏死因子α(TNF-α)处理人视网膜微血管内皮细胞(HRMEC)构建细胞损伤模型,分为model组(0 μmol/L CTS处理)、model+CTS(High)组(40 μmol/L CTS处理)、model+CTS(Medium)组(20 μmol/L CTS处理)、model+CTS(Low)组(10 μmol/L CTS处理);另设正常HRMEC为control组(不做任何处理)。HE染色观察大鼠视网膜组织病理状况;qRT-PCR检测大鼠视网膜组织及HRMEC细胞中TNF-α、细胞间黏附分子-1(ICAM-1)、血管内皮生长因子(VEGF)、白细胞介素-1β(IL-1β)的mRNA表达水平;Western blot检测视网膜组织及HRMEC细胞中受体相互作用蛋白2(RIP2)/核因子-κB(NF-κB)/NOD样受体热蛋白结构域相关蛋白3(NLRP3)信号通路相关蛋白和视网膜组织中凋亡蛋白半胱氨酸天冬氨酸蛋白酶(Caspase)-3和Caspase-9表达情况。
结果
2
与糖尿病组相比,CTS能够缓解糖尿病大鼠视网膜病变,抑制视网膜组织中凋亡蛋白Caspase-3和Caspase-9表达,抑制糖尿病大鼠的血管生成能力和视网膜组织中TNF-α、IL-1β表达水平(
P
<
0.05),且呈剂量依赖性。与model组相比,CTS可抑制HRMEC的炎症和血管生成能力,并抑制RIP2/NF-κB/NLRP3信号通路相关蛋白表达(
P
<
0.05),且呈剂量依赖性。
结论
2
CTS通过抑制RIP2/NF-κB/NLRP3信号通路的激活参与调控DR的炎症反应,改善DR。
Objective
2
To explore the role and potential molecular mechanism of cryptotanshinone (CTS) in regulating diabetic retinopathy (DR).
Methods
2
Fifty rats were randomly divided into the control group (treated with normal saline),diabetic group (intraperitoneal injection of 55 mg/kg of streptozotocin to establish a diabetes model),model H-CTS group (treated with 75 μg of CTS after modeling),model M-CTS group (treated with 50 μg of CTS after modeling),and model L-CTS group (treated with 25 μg of CTS after modeling).The human retinal microvascular endothelial cells (HRMEC) were treated with 10 ng/mL tumor necrosis factor-α (TNF-α) to construct cell injury models,and divided into the model group(treated with 0 μmol/L CTS),model+CTS (High) group(treated with 40 μmol/L CTS),model+CTS (Medium) group(treated with 20 μmol/L CTS),and model+CTS (Low) group(treated with 10 μmol/L CTS);and normal HRMECs were set as the control group (without any treatment).HE staining was used to observe the pathological conditions of retinal tissues in rats.qRT-PCR was used to detect the mRNA expression levels of TNF-α,intercellular adhesion molecule-1 (ICAM-1),vascular endothelial growth factor (VEGF),and interleukin-1β (IL-1β) in rat retinal tissues and HRMEC cells.Western blot was used to detect the expression of proteins related to the receptor interacting protein-2 (RIP2)/nuclear factor-kappa B (NF-κB)/NOD-like receptor thermal protein domain associated protein 3 (NLRP3) signaling pathway in retinal tissues and HRMEC cells,and the apoptotic proteins cysteinyl aspartate-specific proteinase(Caspase)-3 and Caspase-9 in retinal tissues.
Results
2
Compared with the diabetic group,CTS could alleviate retinopathy in diabetic rats and inhibit the expression of apoptotic proteins Caspase-3 and Caspase-9 in retinal tissues (
P
<
0.05),and reduce the angiogenesis ability of diabetic rats and the expression levels of TNF-α and IL-1β in retinal tissues in a dose-dependent manner (
P
<
0.05).Compared with the model group,CTS could inhibit the inflammation and angiogenesis ability of HRMEC,and reduce the expression of proteins related to the RIP2/NF-κB/NLRP3 signaling pathway in a dose-dependent manner (
P
<
0.05).
Conclusion
2
CTS participates in regulating the inflammatory response of DR by inhibiting the activation of the RIP2/NF-κB/NLRP3 signaling pathway,thereby improving DR.
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