| 杨黎,王真,杨铁城,等.Ly6Chi单核细胞 PD-L1表达与糖尿病脓毒症小鼠肾损伤关系的研究[J].安徽医药,2026,30(7):1436-1440. |
| Ly6Chi单核细胞 PD-L1表达与糖尿病脓毒症小鼠肾损伤关系的研究 |
| Correlation between PD-L1 expression on Ly6Chi monocytes and renal injury in diabetic mice with sepsis |
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| DOI：10.3969/j.issn.1009-6469.2026.07.032 |
| 中文关键词: 糖尿病并发症 脓毒症 肾损伤 单核细胞 程序性细胞死亡配体 1(PD-L1) 小鼠，近交 C57BL |
| 英文关键词: Diabetes complications Sepsis Kidney injury Monocyte Programmed cell death-ligand 1(PD-L1) Mice,inbred C57BL |
| 基金项目:北京市重点实验室开放课题项目( 2019XFN-KFKT-02) |
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| 中文摘要: |
| 目的观察糖尿病合并脓毒症小鼠肾损伤特点，并初步探讨单核细胞亚型在糖尿病合并脓毒症肾损伤中的作用。方法 2022年 6—12月， 24只 C57BL/6J雄性小鼠按随机数字表法分为非糖尿病鼠假手术组( Sham组)、非糖尿病鼠脓毒症模型组(CLP组)、糖尿病鼠假手术组( DMS组)、糖尿病鼠脓毒症模型组( DMCLP组)，每组 6只；高糖高脂饲料喂养联合链脲佐菌素腹腔注射诱导建立糖尿病小鼠模型，采用盲肠结扎穿孔( cecal ligation and puncture，CLP)方法建立脓毒症小鼠模型， CLP术后 24 h采用流式细胞术观察各组小鼠高表达 Ly6C单核细胞(Ly6Chi)即经典单核细胞亚型及其表面程序性死亡配体 1(PD-L1)表达，酶联免疫吸附分析(ELISA)检测各组小鼠血清白细胞介素 -6(IL-6)肿瘤坏死因子 α(TNF-α)和单核细胞趋化蛋白 -1(MCP-1)表达，全自动生化检测仪检测各组小鼠血尿素氮( BUN)和血肌酐水平，、苏木精 -伊红( HE)染色观察小鼠肾组织损伤情况，免疫组织化学法( IHC)观察肾组织 F4/80表达量。结果与 CLP组小鼠相比， DMCLP组小鼠 Ly6Chi单核细胞百分比升高［( 97.18±2.84)%比( 92.70±3.31)%］Ly6Chi单核细胞表面 PD-L1表达升高［( 96.43±4.43)%比( 88.82±10.18)%］，血清炎症因子 IL-6、TNF-α和 MCP-1表达明显上升，［( 261.14±15.49)ng/L比( 217.79±13.83)ng/L、(206.6±52.58)μg/L比( 135.55±27.74)μg/L、(256.76±73.41) μg/L比( 117.01±37.74)μg/L］，BUN、血肌酐升高［( 35.79±5.93)mmol/L比( 14.13±4.34)mmol/L、(74.46±9.99)μmol/L比( 25.21±4.73)μmol/L］，肾组织炎性渗出增加，巨噬细胞浸润增加。结论糖尿病合并脓毒症小鼠肾损伤较非糖尿病脓毒症小鼠更为严重，可能与高血糖时经典单核细胞 PD-L1表达升高并促进炎症因子表达有关。 |
| 英文摘要: |
| Objective To observe the characteristics of kidney injury in diabetic mice with sepsis, and to investigate the role of mono-cyte subset in kidney injury in diabetic mice with sepsis.Methods From June to December 2022, 24 male C57BL/6J mice were ran-domly divided into 4 groups (n=6): non-diabetic mice sham group (Sham group), non-diabetic mice CLP group (CLP group), diabeticmice sham group (DMS group),diabetic mice CLP group (DMCLP group). A diabetic mouse model was constructed by feeding high-sug-ar and high-fat diet combined with intraperitoneal streptozotocin (STZ) injection, and a mouse model of sepsis was established using ce-cal ligation and puncture (CLP). At 24 hours after CLP surgery, flow cytometry was used to observe the classical monocyte subset char-acterized by high expression of Ly6C (Ly6Chi) and the expression of programmed death-ligand 1 (PD-L1) on their surface in each group of mice. The expressions of inflammatory factors interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and monocyte chemoattractant protein-1 (MCP-1) in each group were detected by enzyme-linked immunosorbent assay (ELISA). The levels of serum blood urea nitro-gen (BUN) and creatininen in each group were detected by automatic biochemical analyzer. The pathological damage of renal tissue wasobserved by hematoxylin-eosin (HE) staining, and the expression of F4/80 in renal tissue was observed by immunohistochemistry (IHC). Results Our findings demonstrated a significant increase in the proportion of Ly6Chi monocytes and the expression of PD-L1 on Ly6Chi monocytes in the DMCLP group compared to the CLP group [(97.18±2.84) % vs. (92.70±3.31) %, (96.43±4.43) % vs. (88.82± 10.18) %]. Additionally, there was a notable upregulation in serum levels of IL-6, TNF-α and MCP-1 [(261.14±15.49) ng/L vs. (217.79± 13.83) ng/L, (206.6±52.58) μg/L vs. (135.55±27.74) μg/L, (256.76±73.41) μg/L vs. (117.01±37.74) μg/L], along with levels of BUN and serum creatinine [(35.79±5.93) mmol/L vs. (14.13±4.34) mmol/L, (74.46±9.99) μmol/L vs. (25.21±4.73) μmol/L]. Furthermore, re-nal inflammatory exudation and macrophage infiltration were observed to be increased. Conclusion The kidney injury of diabetic mice with sepsis was more serious than that of non-diabetic mice with sepsis, potentially attributed to the upregulation of PD-L1 expres-sion on classical monocytes and the promotion of inflammatory factor expression. |
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