石墨烯发热膜热疗改善小鼠冻伤的作用及机制

doi:10.12122/j.issn.1673-4254.2025.03.10

南方医科大学学报 ›› 2025, Vol. 45 ›› Issue (3): 522-530.doi: 10.12122/j.issn.1673-4254.2025.03.10

• • 上一篇

石墨烯发热膜热疗改善小鼠冻伤的作用及机制

张金水¹^,²^,³(), 李硕², 魏栋栋², 成昕², 邓云¹^,³(), 张有志²()

^1.安徽理工大学第一附属医院（淮南市第一人民医院），安徽淮南 232007
^2.军事医学研究院//国家安全特需药品全国重点实验室，北京 100850
^3.安徽理工大学医学院，安徽淮南 232001

收稿日期:2024-07-10 出版日期:2025-03-20 发布日期:2025-03-28
通讯作者: 邓云,张有志 E-mail:1254604317@qq.com;yunfree196@yeah.net;bcczyz@163.com
作者简介:张金水，硕士，E-mail: 1254604317@qq.com
基金资助:
安徽理工大学医学专项培育项目(YZ2023H2C015);国家自然科学基金(81274117)

Protective effect of graphene heating film far-infrared hyperthermia against frostbite in mice

Jinshui ZHANG¹^,²^,³(), Shuo LI², Dongdong WEI², Xin CHENG², Yun DENG¹^,³(), Youzhi ZHANG²()

^1.The First Affiliated Hospital of Anhui University of Science and Technology (Huainan First People's Hospital), Huainan 232007, China
^2.Academy of Military Medical Sciences, National Key Laboratory of National Security Essential Drugs, Beijing 100850, China
^3.School of Medicine, Anhui University of Science and Technology, Huainan 232001, China

Received:2024-07-10 Online:2025-03-20 Published:2025-03-28
Contact: Yun DENG, Youzhi ZHANG E-mail:1254604317@qq.com;yunfree196@yeah.net;bcczyz@163.com
Supported by:
National Natural Science Foundation of China(81274117)

摘要/Abstract

摘要：

目的研究石墨烯发热膜热疗对不同冻伤模型小鼠的防护作用，以及对微循环和凝血功能的影响。方法远红外干预实验：FIR热疗7 d，4 h/d，10只雄性ICR小鼠随机分为石墨烯-FIR组、碳纤维-FIR组（n=5），干预结束后，红外成像检测小鼠体表温度。冷暴露动物模型建立实验：76只雄性C57BL/6J小鼠随机分为2个实验分组，每个实验组分为对照组（n=8）、模型组（n=10）、石墨烯-远红外（FIR）组（n=10）、碳纤维-FIR组（n=10）。FIR热疗干预7 d，4 h/d。采用急性寒冷暴露（4 ℃，4 h）和间歇性寒冷暴露（4 ℃，4 h/d，3 d），制备急性冷暴露和间歇性冷暴露小鼠模型，并进行肛温检测。液氮法制备冻伤模型及评价：24只雄性ICR小鼠随机分为模型组、石墨烯-FIR组、碳纤维-FIR组（n=8）。采用液氮冷冻法直接冻伤皮肤，制备冻伤模型。造模前FIR热疗干预7 d，4 h/d，造模后第3、6天对冻伤区域表观指标进行评分。角叉菜胶诱发小鼠尾部血栓模型建立及评价：40只雄性ICR小鼠随机分为对照组、模型组、石墨烯-FIR组、碳纤维-FIR组、哌唑嗪阳性药组（n=8）。腹腔注射角叉菜胶（2.5 mg/kg）进行尾部血栓模型的制备。造模前FIR热疗干预7 d，4 h/d。造模24 h后测量尾部血栓长度，通过HE检测病理变化，取血检测各组小鼠血栓因子：6-keto-PGF1α、TXB₂、t-PA，以及炎症因子：IL-6、IL-1β、TNF-α的变化。结果冷暴露实验结果显示，与模型组相比，石墨烯-FIR组小鼠肛温升高。液氮冻伤实验结果表明，石墨烯-FIR热疗能够降低小鼠冻伤区域表观评分（P<0.01），改善冻伤程度，且效果优于碳纤维-FIR组。角叉菜胶诱导血栓实验结果显示，与模型组比较，石墨烯-FIR组黑尾长度缩短（P<0.05），血栓面积减少，尾部血栓处血流灌注量升高（P<0.01）；血栓因子TXB₂和炎症因子TNF-α、IL-6水平下降（P<0.01），6-keto-PGF1α和t-PA水平升高（P<0.05）。结论石墨烯发热膜热疗通过促进血液微循环，降低炎症发生，改善凝血功能障碍来改善不同程度冻伤引起的组织损伤。

关键词: 石墨烯发热膜, 远红外, 冻伤, 微循环, 炎症

Abstract:

Objective To investigate the protective effects of graphene heating film far-infrared (FIR) hyperthermia therapy against frostbite in mice and its impacts on microcirculation and coagulation function. Methods Seventy-six C57BL/6J mice were randomized into control, model, graphene-FIR, and carbon fiber-FIR groups. After 7-day FIR intervention (4 h/day), the mice were subjected to acute (4 ℃, 4 h) and intermittent (4 ℃, 4 h/day for 3 days) cold exposure and the changes in rectal temperature were monitored. In liquid nitrogen frostbite experiment, 24 ICR mice were divided into model, graphene-FIR, and carbon fiber-FIR groups, and after a 7-day FIR pretreatment (4 h/day), the liquid nitrogen frostbite models were established and apparent scores of the wounds were assessed on days 3 and 6 after modeling. In carrageenan-induced thrombosis experiment, 40 ICR mice were allocated to control, model, graphene-FIR, carbon fiber-FIR, and prazosin groups to test the effect of a 7-day FIR intervention on thrombosis induced by intraperitoneal carrageenan injection (2.5 mg/kg) by measuring thrombus length, blood perfusion, and serum biomarkers (6-keto-PGF1α, TXB2, t-PA, IL-6, IL-1β, TNF‑α) 24 h after the injection. Results The mice in graphene-FIR group showed significantly elevated rectal temperature in cold exposure tests. In mice with liquid nitrogen-induced frostbite, graphene-FIR treatment significantly reduced the wound scores and reduced frostbite area, producing better effects than carbon fiber. In mice with carrageenan-induced thrombosis, graphene-FIR treatment significantly decreased tail thrombosis length and thrombosis area, increased blood perfusion, lowered serum levels of TXB2, TNF-α and IL-6, and increased the levels of 6-keto-PGF1α and t-PA. Conclusion Graphene heating film FIR therapy can alleviate frostbite injury in mice by improving microcirculation, suppressing thrombosis and inflammatory responses, and reducing coagulation dysfunction.

Key words: graphene heating film, far-infrared therapy, frostbite, microcirculation, inflammation

张金水, 李硕, 魏栋栋, 成昕, 邓云, 张有志. 石墨烯发热膜热疗改善小鼠冻伤的作用及机制[J]. 南方医科大学学报, 2025, 45(3): 522-530.

Jinshui ZHANG, Shuo LI, Dongdong WEI, Xin CHENG, Yun DENG, Youzhi ZHANG. Protective effect of graphene heating film far-infrared hyperthermia against frostbite in mice[J]. Journal of Southern Medical University, 2025, 45(3): 522-530.

图/表 9

图1 实验流程

Fig. 1 Procedures of infrared thermal imaging experiment (A), acute and intermittent cold exposure experiment (B-C), liquid nitrogen frostbite experiment (D) and carrageenan-induced thrombosis experiment (E).

图2 石墨烯和碳纤维材料学性质

Fig. 2 Characterization of properties of graphene and carbon fiber materials. A: Schematic diagram of FIR device. B: Electrothermal properties of graphene and carbon fiber. C: Absorption peak of the human body surface (8.0 µm) and FIR emission peaks of graphene (8 µm) and carbon fiber (7.6 µm). D: Peak comparison of graphene, carbon fiber and human body at 7.5-8.5 µm wavelength (graphene: 1.9 W, carbon ﬁber: 1.9 W). E, F: Surface temperature changes and analysis of graphene-FIR and carbon fiber-FIR mice after irradiation. *P<0.05, **P<0.01 between the two groups.

图3 急性冷暴露和间歇性冷暴露后小鼠肛温

Fig.3 Rectal temperature of mice after acute (A) and intermittent cold exposure (B). *P<0.05, **P<0.01 vs NC group, ##P<0.01 vs model group; $$P<0.01 vs Car group.

图4 小鼠冻伤区域图片及冻伤区域温度变化

Fig. 4 Frostbite in the dorsal skin of the mice and temperature changes in the frostbite area (A) and comparison of wound temperatures among the 3 groups (B). ##P<0.01 vs model group.

图5 冻伤小鼠冻伤区域表观评分变化

Fig.5 Changes in apparent score of frostbite area in the mice on the 3rd day (A) and 6th day (B) after frostbite. *P<0.05, **P<0.01 vs model group; #P<0.05, ##P<0.01 vs Gra group.

图6 各组血栓小鼠尾部血栓图片及血栓长度比较

Fig. 6 Thrombus in the tail of the mice (A) and comparison of the length of thrombus among the 4 groups (B). **P<0.01 vs NC group; #P<0.05 vs Model group.

图7 各组小鼠尾部血栓血流灌注量对比及统计分析图

Fig. 7 Blood perfusion images of the mouse tails (A) and comparison of blood perfusion parameters at the root (B) and tail (C) among the 5 groups. **P<0.01 vs NC group; ##P<0.01 vs Model group; $P<0.05, $$P<0.01 vs Car group.

图8 各组血栓小鼠不同的尾部位置HE染色

Fig. 8 HE staining of the tissues of mouse tails taken at 2, 4, and 6 cm from the tail tip in each group (Original magnification: ×200). The blue and red dotted lines show the vessel profile and the thrombi formed in the vein, respectively.

图9 血栓小鼠血清血栓因子及炎症因子水平变化

Fig. 9 Changes of serum thrombus factors 6-keto-PGF1α, TXB2 and t-PA (A-C) and the inflammatory factors TNF-α, IL-6 and IL-1β (D-F). **P<0.01 vs NC group; #P<0.05, ##P<0.01 vs Model group.

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石墨烯发热膜热疗改善小鼠冻伤的作用及机制

Protective effect of graphene heating film far-infrared hyperthermia against frostbite in mice

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