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1.上海中医药大学附属岳阳中西医结合医院(上海 200437)
2.上海中医药大学附属龙华医院(上海 200032)
陈昊,女,硕士,医师,主要从事中医药防治肾脏病的基础研究工作
李屹,主任医师,博士研究生导师; E-mail:lh1260@shutcm.edu.cn
收稿:2025-12-11,
纸质出版:2026-06-10
移动端阅览
陈昊,罗磊,刘珊,等.艾灸延缓肾小管间质纤维化的作用与机制初探[J].上海中医药杂志,2026,60(6):63-72.
CHEN Hao,LUO Lei,LIU Shan,et al.Preliminary study on effect and mechanism of moxibustion in delaying renal tubulointerstitial fibrosis[J].Shanghai Journal of Traditional Chinese Medicine,2026,60(6):63-72.
陈昊,罗磊,刘珊,等.艾灸延缓肾小管间质纤维化的作用与机制初探[J].上海中医药杂志,2026,60(6):63-72. DOI: 10.16305/j.1007-1334.2026.z20251211003.
CHEN Hao,LUO Lei,LIU Shan,et al.Preliminary study on effect and mechanism of moxibustion in delaying renal tubulointerstitial fibrosis[J].Shanghai Journal of Traditional Chinese Medicine,2026,60(6):63-72. DOI: 10.16305/j.1007-1334.2026.z20251211003.
目的
2
探讨艾灸干预单侧输尿管结扎(UUO)小鼠肾小管间质纤维化(TIF)的作用机制。
方法
2
C57BL/6J小鼠通过UUO法建立TIF小鼠模型,分为假手术(Sham)组、假手术加艾灸(Sham+Moxa)组、模型(Model)组和模型加艾灸(Moxa)组。通过苏木精-伊红染色、天狼猩红染色、马松染色观察肾组织病理变化,测定胶原容积分数(CVF)并结合免疫组织化学法检测α-平滑肌肌动蛋白(α-SMA)、Ⅰ型胶原蛋白(Col Ⅰ)以评估TIF程度;采用免疫荧光法检测肾小管缺氧诱导因子-1α(HIF-1α)评估肾小管缺血缺氧状态,检测血小板反应蛋白-1(TSP-1)和血小板内皮细胞黏附分子-1[PECAM-1(又称CD31)]评估血管损伤,双染法检测延缓衰老蛋白(Klotho)/CD31以评估肾小管周围毛细血管(PTC)内皮细胞Klotho表达;逆转录实时定量聚合酶链反应(RT-qPCR)法测定纤维化相关因子蜗牛家族转录抑制因子1(
Snail1
)、CCAAT增强子结合蛋白delta(
Cebpd
)mRNA表达。
结果
2
艾灸可显著改善肾组织肾小管萎缩、管腔狭窄,减少细胞外基质增生与间质胶原纤维表达,降低CVF。免疫组织化学显示,艾灸能降低肾小管间质α-SMA、ColⅠ阳性表达。免疫荧光显示,艾灸能降低肾小管间质HIF-1α、TSP-1阳性表达,增加PTC内皮细胞CD31与Klotho阳性表达。RT-qPCR显示,艾灸能降低肾组织
Snail1
、
Cebpd
的mRNA表达。
结论
2
艾灸可通过上调PTC内皮细胞Klotho表达,改善肾小管上皮细胞缺血缺氧状态,抑制纤维化相关因子表达,从而延缓TIF进展。
Objective
2
To investigate the mechanism of moxibustion intervention on renal tubulointerstitial fibrosis (TIF) in mice with unilateral ureteral obstruction (UUO).
Methods
2
A TIF mouse model was established using the UUO method in C57BL/6J mice. The mice were divided into Sham operation (Sham) group, Sham operation plus moxibustion (Sham+Moxa) group, Model group, and Model plus moxibustion (Moxa) group. Pathological changes in renal tissue were observed using Hematoxylin-Eosin, Sirius Red and Masson's staining. Collagen volume fraction (CVF) was measured, and immunohistochemistry was performed to detect α-smooth muscle actin (α-SMA), type Ⅰ collagen (Col Ⅰ), so as to evaluate the degree of TIF. The immunofluorescence method was used to detect hypoxia-inducible factor-1α (HIF-1α) in renal tubules to assess the ischemic-hypoxic state of renal tubules; Thrombospondin (TSP-1) and platelet endothelial cell adhesion molecule-1 (PECAM-1/CD31) were detected to evaluate vascular injury; Double staining with the anti-aging protein Klotho/CD31 was detected to assess the Klotho expression in the endothelial cells of peritubular capillaries (PTC) around the renal tubules. Real-time fluorescence quantitative reverse transcription polymerase chain reaction (RT-qPCR) was used to measure the mRNA expression of fibrosis-related factors Snail family transcriptional repressor 1 (
Snail1
) and CCAAT enhancer binding protein delta (
Cebpd
).
Results
2
Moxibustion could significantly improve renal tubular atrophy and luminal stenosis, reduce extracellular matrix hyperplasia and interstitial collagen fiber expression, and decrease CVF. Immunohistochemistry showed that moxibustion could reduce the positive expression of α-SMA and ColⅠ in the
renal tubulointerstitium. Immunofluorescence revealed that moxibustion could decrease the positive expression of HIF-1α and TSP-1 in renal tubular epithelial cells and increase the positive expression of CD31 and Klotho in PTC endothelial cells. RT-qPCR demonstrated that moxibustion could downregulate the mRNA expression of
Snail1
and
Cebpd
in renal tissue.
Conclusions
2
Moxibustion delays the progression of TIF by upregulating Klotho expression in PTC endothelial cells, alleviating ischemia and hypoxia in renal tubular epithelial cells, and inhibiting the expression of fibrosis-related factors.
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