
浏览全部资源
扫码关注微信
1.甘肃中医药大学附属医院皮肤科(甘肃 兰州 730000)
2.甘肃中医药大学附属医院小儿骨科(甘肃 兰州 730000)
3.兰州市疾病预防控制中心性病艾滋病防治科(甘肃 兰州 730000)
徐兰萍,女,硕士,副主任医师,主要从事皮肤病学临床研究工作
梁恬,副主任医师;E-mail:1417209908@qq.com
收稿:2024-09-28,
纸质出版:2025-10-10
移动端阅览
徐兰萍,梁恬,陈继军,等.基于“肺与大肠相表里”探究复方嗜酸乳杆菌片联合马齿苋提取液对湿疹大鼠肠道菌群、免疫功能及cAMP/PKA的影响[J].上海中医药杂志,2025,59(10):66-71.
XU Lanping,LIANG Tian,CHEN Jijun,et al.Exploring effects of compound Lactobacillus acidophilus tablets combined with Portulacae Herba extract on intestinal microbiota abundance, immune function, and cAMP/PKA in eczema rats based on theory of "exterior⁃interior relationship between lung and large intestine"[J].Shanghai Journal of Traditional Chinese Medicine,2025,59(10):66-71.
徐兰萍,梁恬,陈继军,等.基于“肺与大肠相表里”探究复方嗜酸乳杆菌片联合马齿苋提取液对湿疹大鼠肠道菌群、免疫功能及cAMP/PKA的影响[J].上海中医药杂志,2025,59(10):66-71. DOI: 10.16305/j.1007-1334.2025.z20240928003.
XU Lanping,LIANG Tian,CHEN Jijun,et al.Exploring effects of compound Lactobacillus acidophilus tablets combined with Portulacae Herba extract on intestinal microbiota abundance, immune function, and cAMP/PKA in eczema rats based on theory of "exterior⁃interior relationship between lung and large intestine"[J].Shanghai Journal of Traditional Chinese Medicine,2025,59(10):66-71. DOI: 10.16305/j.1007-1334.2025.z20240928003.
目的
2
探究复方嗜酸乳杆菌片联合马齿苋提取液对湿疹大鼠肠道菌群、免疫功能及环腺苷酸(cAMP)/蛋白激酶A(PKA)的影响。
方法
2
成年雄性SD大鼠50只随机分为5组(
n
=10):正常组、模型组、复方嗜酸乳杆菌组、马齿苋组及联合组。除正常组外,其余各组均建立湿疹动物模型。造模成功后,复方嗜酸乳杆菌组灌胃复方嗜酸乳杆菌片,马齿苋组灌胃马齿苋提取液,联合组大鼠灌胃复方嗜酸乳杆菌片+马齿苋提取液,正常组和模型组大鼠灌胃等体积的0.9%氯化钠溶液,连续干预14 d。干预结束后:①观察大鼠背部皮损情况,记录搔抓次数;②采用酶联免疫吸附分析(ELISA)法检测外周血γ干扰素(IFN‑γ)及白细胞介素(IL)-4水平;③16
S rRNA法检测肠道菌群丰度;④采用苏木精-伊红(HE)染色法观察皮损组织病理形态;⑤Western blot法检测cAMP、PKA蛋白水平。
结果
2
①正常组大鼠皮肤为淡红色,细致滑嫩,质地柔软,皮肤纹理清晰可见。模型组大鼠背部皮损明显,可见皮肤红斑、浸润、鳞屑等,符合建模特征。与模型组比较,其余用药组大鼠背部皮损明显好转,以联合组改善最为显著。与正常组比较,模型组大鼠搔抓次数增多(
P
<
0.05)。与模型组比较,复方嗜酸乳杆菌组、马齿苋组及联合组大鼠搔抓次数减少(
P
<
0.05)。与复方嗜酸乳杆菌组及马齿苋组比较,联合组大鼠搔抓次数均减少(
P
<
0.05)。②与正常组比较,模型组大鼠IL-4水平升高(
P
<
0.05),IFN-γ水平降低(
P
<
0.05)。与模型组比较,复方嗜酸乳杆菌组及马齿苋组大鼠IL-4水平降低(
P
<
0.05),IFN-γ水平升高(
P
<
0.05)。与复方嗜酸乳杆菌组及马齿苋组比较,联合组大鼠IL-4水平降低(
P
<
0.05),IFN-γ水平升高(
P
<
0.05)。③与正常组比较,模型组厚壁菌门丰度增加;与模型组比较,复方嗜酸乳杆菌组、马齿苋组及联合组厚壁菌门丰度均降低,其中以联合组厚壁菌门丰度最低。④HE染色可见:正常组大鼠表皮角化正常,真皮乳头层未见水肿和炎症细胞浸润;模型组大鼠存在表皮角化,且存在大量炎症细胞浸润,部分伴随纤维增生及血管增生;复方嗜酸乳杆菌组、马齿苋组及联合组大鼠表皮炎症细胞逐渐消失,皮肤结构逐渐清楚,联合组大鼠仅在真皮层可见到少许炎症,水肿消失,病理形态改善程度最佳。⑤与正常组比较,模型组大鼠cAMP、PKA蛋白水平降低(
P
<
0.05)。与模型组比较,复方嗜酸乳杆菌组大鼠cAMP、PKA蛋白水平升高(
P
<
0.05)。与复方嗜酸乳杆菌组比较,马齿苋组大鼠cAMP、PKA蛋白水平升高(
P
<
0.05)。与复方嗜酸乳杆菌组及马齿苋组比较,联合组大鼠cAMP、PKA蛋白水平升高(
P
<
0.05)。
结论
2
复方嗜酸乳杆菌片联合马齿苋提取液可改善湿疹大鼠肠道菌群紊乱,恢复T辅助细胞Th1/Th2免疫平衡,并通过激活cAMP/PKA信号通路而缓解皮损。
Objective
2
To investigate the effects of compound
Lactobacillus acidophilus
tablets (CLAT) combined with Portulacae Herba extract (POE) on intestinal microbiota, immune function, and the cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA) pathway in rats with eczema.
Methods
2
Fifty adult male SD rats were randomly divided into five groups (
n
=10 per group): normal control, model, CLAT, POE, and combination (CLAT+POE) groups. Eczema models were established in all groups except the normal control group. After successful modeling, interventions were administered via gavage for 14 days: rats in the CLAT group received CLAT suspension, those in the POE g
roup received POE solution, those in the combination group received CLAT+POE, and rats in the normal control and model groups were given 0.9% NaCl solution. After intervention, the following assessments were conducted: ①skin lesions on the back and scratching frequency of rats; ②serum interferon-γ (IFN-γ) and interleukin-4 (IL-4) levels via enzyme-linked immunosorbent assay (ELISA); ③intestinal microbiota abundance via 16S rRNA sequencing; ④histopathology of lesional skin via hematoxylin and eosin (HE) staining; ⑤ cAMP and PKA protein levels via Western blot.
Results
2
①The skin of normal group rats appeared light red, delicate, and smooth, with soft and clear skin texture. The back skin of model group rats showed obvious erythema, infiltration, scales, etc., consistent with eczema modeling characteristics. Compared with the model group, skin lesions on the back of rats in the other treatment groups improved significantly, with the most prominent improvement in the combination group. The scratching frequency was decreased in the CLAT, POE, and combination groups compared with the model group (
P
<
0.05), and was further reduced in the combination group compared with the CLAT or POE group (
P
<
0.05). ②Compared with the normal group, the model group exhibited increased IL-4 levels and decreased IFN-γ levels (
P
<
0.05). Compared with the model group, IL-4 levels were decreased and IFN-γ levels were increased in the CLAT and POE groups (
P
<
0.05); moreover, the combination group showed lower IL-4 levels and higher IFN-γ levels than the CLAT or POE group (
P
<
0.05). ③Model rats had higher
Firmicutes
abundance than normal rats; all treatment groups reduced
Firmicutes
, with the combination group showing the greatest efficacy. ④HE staining revealed that rats in the normal group had normal epidermal keratinization, and no edema or inflammatory cell infiltration was observe
d in the dermal papilla layer. In contrast, model group rats exhibited abnormal epidermal keratinization and abundant inflammatory cell infiltration, partially accompanied by fibrosis and vascular proliferation. In the CLAT, POE, and combination groups, inflammatory cells in the epidermis gradually disappeared, and skin structure gradually normalized; notably, the combination group showed only slight dermal inflammation and no edema, presenting the best pathological improvement. ⑤Compared with the normal group, cAMP and PKA protein levels were decreased in the model group (
P
<
0.05). Compared with the model group, cAMP and PKA levels were increased in the CLAT group (
P
<
0.05), further increased in the POE group compared with the CLAT group (
P
<
0.05), and the combination group showed higher levels than the CLAT or POE group (
P
<
0.05).
Conclusion
2
The combination of CLAT and POE alleviates eczema by modulating intestinal microbiota, restoring the T helper cell Th1/Th2 balance, and activating the cAMP/PKA pathway, thereby synergistically enhancing therapeutic effects.
THYSSEN J P , SCHUTTELAAR M L A , ALFONSO J H , et al . Guidelines for diagnosis, prevention, and treatment of hand eczema [J]. Contact Dermatitis , 2022 , 86 ( 5 ): 357 - 378 .
ZHANG L , LIN S , ZHENG Y , et al . Matrine regulates Th1/Th2 balance to treat eczema by upregulating Interferon- γ [J]. J Nanosci Nanotechnol , 2020 , 20 ( 6 ): 3378 - 3386 .
丁冬梅 , 费建飚 . 双歧杆菌联合肤痔清软膏治疗儿童湿疹的疗效及对患儿肠道菌群、免疫功能的影响 [J]. 海南医学 , 2021 , 32 ( 19 ): 2533 - 2536 .
GUAN Q , WANG Z , HU K , et al . Melatonin ameliorates hepatic Ferroptosis in NAFLD by inhibiting ER stress via the MT2/cAMP/PKA/IRE1 signaling pathway [J]. Int J Biol Sci , 2023 , 19 ( 12 ): 3937 - 3950 .
WITTMANN M , HELLIWELL P S . Phosphodiesterase 4 inhibition in the treatment of psoriasis, psoriatic arthritis and other chronic inflammatory diseases [J]. Dermatol Ther (Heidelb) , 2013 , 3 ( 1 ): 1 - 15 .
孙卓然 , 李静 . 基于“肺与大肠相表里”理论推拿治疗小儿湿疹探析 [J]. 中医外治杂志 , 2023 , 32 ( 2 ): 121 - 123 .
韩晨曦 . 益生菌的早期应用对新生儿湿疹的预防作用 [D]. 唐山 : 华北理工大学 , 2019 .
武亦阁 , 贺乙 , 范丽娜 , 等 . 消风散及其拆方对急性湿疹模型豚鼠表皮通透屏障功能障碍的影响 [J]. 中医杂志 , 2022 , 63 ( 14 ): 1374 - 1380 .
黄继汉 , 黄晓晖 , 陈志扬 , 等 . 药理试验中动物间和动物与人体间的等效剂量换算 [J]. 中国临床药理学与治疗学 , 2004 , 9 ( 9 ): 1069 - 1072 .
李奕蓁 , 柳越冬 . 基于“肺与大肠相表里”理论从血瘀角度探析溃疡性结肠炎 [J]. 上海中医药杂志 , 2025 , 59 ( 4 ): 25 - 29 .
林羽贞 , 王钇杰 , 武洪辉 , 等 . 基于“肺与大肠相表里”论王有鹏教授治疗寒地儿童湿疹经验 [J]. 中国中西医结合儿科学 , 2024 , 16 ( 6 ): 540 - 543 .
文文兵 , 林敏 , 张浩 , 等 . 益生菌联合糖皮质激素治疗婴儿湿疹的疗效观察和免疫学机制分析 [J]. 实用中西医结合临床 , 2023 , 23 ( 22 ): 35 - 38 .
景明夷 . 文氏马齿苋汤治疗急性湿疹(湿热蕴肤证)临床观察及机制研究 [D]. 成都 : 成都中医药大学 , 2023 .
胡一梅 , 葛一漫 , 王华 , 等 . 马齿苋对急性湿疹瘙痒的干预研究 [J]. 天然产物研究与开发 , 2017 , 29 ( 12 ): 2017 - 2023 .
金真率 . 子母配穴针刺联合中药对亚急性湿热浸淫型湿疹的疗效观察 [D]. 上海 : 上海中医药大学 , 2020 .
邹文君 , 王宝成 , 都荣 , 等 . 基于从脾治皮、分消走泄运用一和三清小儿推拿治疗婴幼儿湿疹 [J]. 中国中医药现代远程教育 , 2020 , 18 ( 13 ): 42 - 45 .
WEN J , CHENG S , WANG R , et al . Group 2 innate lymphoid cells boost CD8 + T-cell activation in anti-tumor immune responses [J]. Oncoimmunology , 2023 , 12 ( 1 ): 2243112 .
张维维 , 章惠彬 , 刘云凤 , 等 . 湿疹患儿肠道菌群改变及其与Th1/Th2、Th17/Treg免疫平衡的相关关系 [J]. 全科医学临床与教育 , 2019 , 17 ( 6 ): 526 - 528 .
王若涵 . 肠道菌群紊乱模型小鼠皮肤湿疹样改变的相关机制研究 [D]. 桂林 : 桂林医学院 , 2014 .
胡一梅 , 葛一漫 , 雍江堰 , 等 . 马齿苋提取液通过IL-4途径对急性湿疹大鼠皮肤屏障功能和免疫反应的调控作用 [J]. 时珍国医国药 , 2019 , 30 ( 8 ): 1793 - 1795 .
邹瑾 , 景明夷 , 朱宝华 , 等 . 文氏马齿苋汤对急性湿疹小鼠血清IgE、IL-2和IL-5的影响 [J]. 中医药信息 , 2023 , 40 ( 12 ): 14 - 17 .
王首帆 , 徐宜厚 , 徐爱琴 , 等 . 黄芩苷调节cAMP/PKA/CREB信号通路对湿疹大鼠皮肤屏障功能的影响 [J]. 天津医药 , 2024 , 52 ( 2 ): 148 - 153 .
0
浏览量
0
下载量
0
CSCD
0
CNKI被引量
关联资源
相关文章
相关作者
相关机构
沪公网安备 31011502015228号