摘要
目的探究麻黄升浮药性和葶苈子沉降药性的潜在靶点。方法将340只大鼠采用随机数字表法分为风寒表证模型组80只、风水水肿模型组90只、痰饮停聚模型组90只、肺水模型组80只,各组大鼠按体质量均衡原则及造模需要再行分组。采用吹风加寒冷刺激构建大鼠风寒表证模型,分为正常对照组、风寒表证组、麻黄组、生物碱组、多糖组、非生物碱组和通宣理肺丸组7组,各组均连续灌胃4天;采用尾静脉注射盐酸多柔比星联合吹风刺激构建大鼠风水水肿模型,分为正常对照组、风水水肿组、麻黄组、生物碱组、多糖组、非生物碱组和通宣理肺丸组7组,各组均连续灌胃21天;采用腹腔注射卵白蛋白联合雾化激发构建大鼠痰饮停聚模型,分为正常对照组、痰饮停聚组、葶苈子组、黄酮苷组、黄酮苷元组、低聚糖组、多糖组和脂肪油组8组,各组均连续灌胃7天;通过胸腔注射角叉菜胶构建大鼠肺水模型,分为正常对照组、肺水组、葶苈子组、黄酮苷组、黄酮苷元组、低聚糖组、多糖组和脂肪油组8组,各组均连续灌胃7天。灌胃完成后检测各模型毒蕈碱乙酰胆碱受体M3(CHRM3)、毒蕈碱乙酰胆碱受体M1(CHRM1)和过氧化物酶体增殖物激活受体γ(PPAR-γ)的mRNA水平;检测风寒表证和风水水肿模型CHRM3的蛋白表达,痰饮停聚和肺水模型PPAR-γ的蛋白表达。结果与风寒表证组相比,麻黄组、通宣理肺丸组和生物碱组CHRM3的蛋白及mRNA水平,麻黄组CHRM1的mRNA水平显著升高,非生物碱组CHRM3,通宣理肺丸组和非生物碱组CHRM1及麻黄组、通宣理肺丸组、生物碱组和多糖组PPAR-γ的mRNA水平显著降低(P<0.05或P<0.01)。与风水水肿组相比,麻黄组、通宣理肺丸组和生物碱组CHRM3的蛋白及mRNA水平,麻黄组和通宣理肺丸组CHRM1的mRNA水平,通宣理肺丸组、生物碱组、非生物碱组和多糖组PPAR-γ的mRNA水平显著升高,麻黄组PPAR-γ的mRNA水平显著降低(P<0.05或P<0.01)。与痰饮停聚组相比,低聚糖组CHRM3的mRNA水平,葶苈子组、低聚糖组、黄酮苷组和脂肪油组PPAR-γ的蛋白及mRNA水平显著升高,脂肪油组和黄酮苷元组CHRM1的mRNA水平显著降低(P<0.01)。与肺水组相比,葶苈子组CHRM3的mRNA水平、多糖组PPAR-γ的mRNA水平显著降低,低聚糖组、脂肪油组和多糖组CHRM3的mRNA水平,葶苈子组、黄酮苷组、低聚糖组和脂肪油组PPAR-γ的蛋白及mRNA水平,多糖组和黄酮苷元组CHRM1的mRNA水平显著升高(P<0.05或P<0.01)。结论药性升浮的麻黄及生物碱组分和通宣理肺丸可显著促进病位在表的风寒表证和风水水肿模型大鼠CHRM3的表达,其可能为麻黄升浮药性的潜在作用靶点之一;药性沉降的葶苈子、黄酮苷、低聚糖和脂肪油可显著促进病位在里的痰饮停聚和肺水模型大鼠PPAR-γ的表达,其可能为葶苈子沉降药性的潜在作用靶点之一。
Objective To Explore the potential targets of the ascending and floating nature of Mahuang(Herba Ephedrae)as well as the descending and sinking nature of Tinglizi(Semen Descurainiae seu Lepidii).Methods Totally 340 rats were randomly divided into wind-cold exterior pattern model group(n=80),wind-water edema model group(n=90),phlegm-rheum retention model group(n=90),and pulmonary edema model group(n=80).Further grouping was performed according to the principle of weight balance and modeling needs.The model of wind-cold exterior pattern was constructed by blowing wind and cold stimulation,and the rats were further divided into normal control group,wind-cold exterior pattern group,Mahuang group,alkaloid group,polysaccharide group,non-alkaloid group and Tongxuan Lifei Pill(通宣理肺丸)group.All groups were given continous gavage for four days.The wind-water edema rat model was established by tail vein injection of adriamycin plus blowing wind,and the rats were divided into normal control,wind-water edema,Mahuang,alkaloid,polysaccharide,non-alkaloid and Tongxuan Lifei Pill groups,which were all administered with continuous gavage for 21 days.The phlegm-rheum retention rat model was established through intraperitoneal injection of ovalbumin and with atomization,and the modeled rats were divided into normal control,phlegm-rheum retention,Tinglizi,flavonoid glycoside,flavonoid aglycones,oligosaccharide,polysaccharide and fatty oil groups,which were all given intragastric administration continuously for 7 days.The pulmonary edema model was established by pleural injection of carrageenan,and the rats were divided into normal control,pulmonary edema,Tinglizi,flavonoid glycoside,flavonoid aglycones,oligosaccharide polysaccharide and fatty oil groups,all for 7 days of intragastric administration continuously.The mRNA levels of muscarinic acetylcholine receptor M3(CHRM3),muscarinic acetylcholine receptor M1(CHRM1)and peroxisome proliferator-activated receptorγ(PPAR-γ)were detected.The protein expression of CHRM3 in wind-cold exterior pattern and wind-water edema model,and the protein expression of PPAR-γin phlegm-rheum retention and pulmonary edema model were detected.Results Compared to those in the wind-cold exterior pattern group,the protein and mRNA level of CHRM3 in the Mahuang,Tongxuan Lifei Pill and alkaloid groups,as well as the mRNA level of CHRM1 in the Mahuang group significantly increased,while the level of CHRM3 in the non-alkaloid group,the CHRM1 level in the Tongxuan Lifei Pill and non-alkaloid groups,and the mRNA level of PPAR-γin the Mahuang,Tongxuan Lifei Pill,alkaloid and polysaccharide groups significantly decreased(P<0.01 or P<0.05).Compared to those in the wind-water edema group,the protein and mRNA level of CHRM3 in the Mahuang,Tongxuan Lifei Pill and alkaloid groups,the mRNA level of CHRM1 in the Mahuang and Tongxuan Lifei Pill groups,as well as the mRNA level of PPAR-γin the Tongxuan Lifei Pill,alkaloid,non-alkaloid and polysaccharide groups significantly increased,while the mRNA level of PPAR-γin the Mahuang group significantly decreased(P<0.01 or P<0.05).Compared to those in the phlegm-rheum retention group,the mRNA level of CHRM3 in the oligosaccharide group,and the protein and mRNA level of PPAR-γin the Tinglizi,oligosaccharide group,flavonoid glycoside group and fatty oil group significantly increased,while the mRNA level of CHRM1 in the fatty oil group and flavonoid aglycon group were reduced(P<0.01).Compared to those in the pulmonary edema group,the mRNA level of CHRM3 in the Tinglizi group,and the mRNA level of PPAR-γin the polysaccharide group were significantly reduced,while the mRNA level of CHRM3 in the oligosaccharide group,fatty oil group and polysaccharide group,the mRNA level of PPAR-γin the Tinglizi group,flavonoid glycoside group,oligosaccharide group and fatty oil group,and the mRNA level of CHRM1 in the polysaccharide group and flavonoid aglycon group increased(P<0.01 or P<0.05).Conclusion Mahuang of ascending and floating nature,alkaloid and Tongxuan Lifei Pill could increase the expression of CHRM3 in the rats model of wind-cold exterior pattern and wind-water edema where the disease is located at the exterior;CHRM3 may be one of the potential targets of the ascending and floating nature of Mahuang.Tinglizi of descending and sinking nature,oligosaccharide,flavonoid glycoside and fatty oil could increase the level of PPAR-γin the model of phlegm-rheum retention and pulmonary edema where the disease is located at the interior;PPAR-γmay be one of the potential targets of descending and sinking nature of Tinglizi.
作者
张贝贝
曾梦楠
王亚玺
张钦钦
王茹
吴媛媛
徐瑞齐
侯颖
王梦梦
冯卫生
郑晓珂
ZHANG Beibei;ZENG Mengnan;WANG Yaxi;ZHANG Qinqin;WANG Ru;WU Yuanyuan;XU Ruiqi;HOU Ying;WANG Mengmeng;FENG Weisheng;ZHENG Xiaoke(Henan University of Chinese Medicine,Zhengzhou,450046)
出处
《中医杂志》
CSCD
北大核心
2023年第3期303-310,共8页
Journal of Traditional Chinese Medicine
基金
国家重点研发计划-中医药现代化研究专项(2019YFC1708800)
河南省高层次人才特殊支持计划“中原千人计划”-中原领军人才(ZYQR201810080)。
关键词
升浮药性
沉降药性
麻黄
葶苈子
风寒表证
风水水肿
痰饮停聚
肺水
ascending and floating nature
descending and sinking nature
Mahuang(Herba Ephedrae)
Tinglizi(Semen Descurainiae seu Lepidii)
wind-cold exterior pattern
wind-water edema
phlegm-rheum retention
pulmonary edema
作者简介
通讯作者:郑晓珂,zhengxk.2006@163.com。
