首页|基于ATP能量代谢探讨金匮敏煎方对肾阳虚慢性荨麻疹大鼠的影响及机制

基于ATP能量代谢探讨金匮敏煎方对肾阳虚慢性荨麻疹大鼠的影响及机制

扫码查看
目的:基于ATP能量代谢探讨金匮敏煎方对肾阳虚慢性荨麻疹的影响及机制.方法:48只SD大鼠按完全随机设计分为空白组,模型组,氯雷他定组,金匮敏煎方低、中、高剂量组,以羟基脲灌胃28d建立肾阳虚模型后开始免疫,在第29、38天用卵白蛋白1 mg与10 g/L氢氧化铝混悬液(共1 mL)腹腔注射致敏建立大鼠肾阳虚慢性荨麻疹模型,从首次免疫后第7天开始,各给药组灌胃相应的药物,连续14d.灌胃结束后用ELISA法测定血清免疫球蛋白E(IgE)、γ-干扰素(IFN-γ)、白细胞介素4(IL-4)、环磷酸腺苷(cAMP)、环磷酸鸟苷(cGMP)、睾酮(T)、促甲状腺激素(TSH)水平,甲苯胺蓝染法观察并计数大鼠皮肤肥大细胞脱颗粒率,免疫组化和Western Blot法检测皮肤P2X7、ENPP3的表达水平,HE染色观察大鼠皮肤、胸腺和睾丸的组织病理学变化.结果:在改善肾阳虚荨麻疹大鼠过敏性炎症方面,与模型组比较,氯雷他定组及金匮敏煎方高、中、低组可显著降低IgE、IL-4水平,提高IFN-γ水平(P<0.05).在抑制皮肤肥大细胞脱颗粒方面,与模型组比较,氯雷他定组及金匮敏煎方高、中、低剂量组肥大细胞脱颗粒率显著降低(P<0.05).在病理组织结构修复方面:与模型组比较,氯雷他定组及金匮敏煎方高、中剂量组对恢复大鼠皮肤结构效果显著,而金匮敏煎方低剂量组对大鼠皮肤结构无明显的改善.金匮敏煎方各组均能够促进大鼠胸腺、睾丸组织的恢复,而氯雷他定对胸腺、睾丸组织结构无明显的修复作用.与模型组比较,金匮敏煎方高、中、低剂量组能显著升高cAMP、T、TSH水平,降低cGMP水平(P<0.05).与模型组比较,金匮敏煎方中、高剂量组大鼠T、TSH水平显著升高(P<0.05).在皮肤P2X7、ENPP3的表达方面:与模型组比较,氯雷他定组及金匮敏煎方高、中剂量组P2X7/ENPP3蛋白表达显著降低(P<0.05).结论:金匮敏煎方主要是通过改善机体能量代谢增加ATP酶活性来发挥疗效,同时可能通过降低IgE含量、升高IFN-γ含量,使皮肤肥大细胞脱颗粒受到限制,从而降低炎症反应.
Discussion on the effects and mechanism of Jingui Minjian Formula on chronic urticaria rats with kidney yang deficiency based on ATP energy metabolism
Objective:To explore the effects and mechanism of Jingui Minjian Formula on chronic urticaria with kidney yang deficiency based on ATP energy metabolism.Methods:A total of 48 SD rats were randomly divided into blank group,model group,loratadine group,low,medium and high dose groups of Jingui Minjian Formula.The model of kidney yang deficiency was established by intragastric administration of hydroxyurea for 28 days,and then the rats were immunized.The model of chronic urticaria with kidney-yang deficiency was established by intraperitoneal injection of 1 mL of ovalbumin 1 mg and 10 g/L aluminum hydroxide suspension on the 29th and 38th days.From the 7th day after the first immunization,each administration group was given corresponding drugs for 14 days.After intragastric administration,the levels of serum immunoglobulin E(IgE),interferon-γ(IFN-γ),interleukin-4(IL-4),cyclic adenosine monophosphate(cAMP),cyclic guanosine monophosphate(cGMP),testosterone(T)and thyroid stimulating hormone(TSH)were determined by ELISA.The degranulation rate of rat skin mast cells was observed and counted by toluidine blue staining.The expression levels of P2X7 and ENPP3 in skin were detected by immunohistochemistry and Western Blot.The histopathological changes of rat skin,thymus and testis were observed by HE staining.Results:In terms of improving allergic inflammation in rats with kidney yang deficiency urticaria,compared with the model group,loratadine group and Jingui Minjian Formula high,medium and low groups could significantly reduce the levels of IgE and IL-4,increase the level of IFN-γ(P<0.05).In terms of inhibiting the degranulation of skin mast cells,compared with the model group,the degranulation rate of mast cells in the loratadine group and the high,medium and low dose groups of Jingui Minjian Formula decreased significantly(P<0.05).In terms of pathological tissue structure repair:compared with the model group,the loratadine group and the high and medium dose groups of Jingui Minjian Formula had a significant effect on restoring the skin structure of rats,while the low dose group of Jingui Minjian Formula had no significant improvement in the skin structure of rats.Each group of Jingui Minjian Formula can promote the recovery of thymus and testicular tissue in rats,while loratadine has no obvious repair effect on thymus and testicular tissue structure.Compared with the model group,the high,medium and low dose groups of Jingui Minjian Formula can significantly increase the levels of cAMP,T and TSH;the levels of cGMP was decreased(P<0.05).Compared with the model group,the levels of T and TSH in the medium and high dose groups of Jinguimin Formula were significantly increased(P<0.05).In terms of the expression of P2X7 and ENPP3 in the skin:compared with the model group,the protein expression of P2X7 and ENPP3 in loratadine group and Jinguimin Formula high and medium dose group were significantly decreased(P<0.05).Conclusion:Jingui Minjian Formula mainly exerts its curative effect by improving the body's energy metabolism and increasing ATPase activity.At the same time,it may limit the degranulation of skin mast cells by reducing IgE content and increasing IFN-γ content,thereby reducing the inflammatory response.

Chronic urticariaKidney yang deficiencyJingui Minjian FormulaP2X7ENPP3

马小娟、马文礼、杨占录、马玉贵、马乾宁、王丽新

展开 >

宁夏医科大学,银川 750000

宁夏少数民族医药现代化教育部重点实验室,银川 750000

宁夏回族自治区中医医院暨中医研究院,银川 750000

慢性荨麻疹 肾阳虚 金匮敏煎方 嘌呤能受体P2X7 外核苷酸磷酸二酯酶3

宁夏教育厅宁夏医科大学中医学一流学科项目宁夏省自然科学基金项目

NXYLXK2017A062018AAC03082

2024

中华中医药杂志
中华中医药学会

中华中医药杂志

CSTPCD北大核心
影响因子:1.135
ISSN:1673-1727
年,卷(期):2024.39(9)