摘要
目的 探讨二术天麻颗粒对临界性高血压(PHT)痰湿证模型大鼠的影响。方法 将WKY大鼠随机分为空白对照组、模型组和二术天麻颗粒高(1 944 mg·kg^(-1)·d^(-1))、中(972 mg·kg^(-1)·d^(-1))、低(486 mg·kg^(-1)·d^(-1))剂量组。采用高盐高脂饮食诱导PHT痰湿证大鼠模型,给予不同剂量二术天麻颗粒连续干预6周。观察各组大鼠活动度、精神状态、粪便性质等证候学指标并记录一般状况评分;测量大鼠体重、Lee’s指数、血压[收缩压(SBP)、舒张压(DBP)、平均动脉压(MAP)];腹主动脉取血,检测血清血脂[总胆固醇(TC)、甘油三酯(TG)、高密度脂蛋白(HDL-C)、低密度脂蛋白(LDL-C)]、炎症因子[C-反应蛋白(CRP)、肿瘤坏死因子-α(TNF-α)、白细胞介素(IL)-1β、IL-6]、氧化应激指标[超氧化物歧化酶(SOD)、丙二醛(MDA)]、血管舒张因子[一氧化氮(NO)]、氧化三甲胺(TMAO)水平及安全性指标[血糖(GLU)、丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST)、肌酐(Cr)、血尿素氮(BUN)];取胸主动脉,HE、Masson染色观察胸主动脉形态。结果 与空白对照组相比,模型组大鼠出现嗜睡懒动、精神不振、大便稀软等痰湿证表现;一般状况评分、体重、Lee’s指数、血压升高(P<0.01),且BP能够保持在130~140/75~80 mm Hg,TC、TG、LDL-C升高(P<0.01),HDL-C下降(P<0.01),CRP、TNF-α、IL-1β增加(P<0.01),SOD活力降低(P<0.01),MDA增加(P<0.01),NO减少(P<0.01),TMAO升高(P<0.01);胸主动脉内膜不规则,少量炎性细胞浸润,中膜厚度增厚,平滑肌细胞排列紊乱,胶原纤维明显增多。与模型组相比,二术天麻颗粒高、中剂量组大鼠痰湿证表现改善;一般状况评分、体重、Lee’s指数、血压降低(P<0.01),TC、TG、LDL-C下降(P<0.01),HDL-C上升(P<0.01),CRP、TNF-α、IL-1β减少(P<0.01),SOD活力升高(P<0.01),MDA减少(P<0.01),NO增多(P<0.01),TMAO减少(P<0.01);胸主动脉内膜较为光滑平整,未见明显炎性浸润,中膜厚度适中,平滑肌细胞排列较为整齐,胶原纤维减少;高剂量二术天麻颗粒效果更显著;各项安全性指标组间均无明显差异(P>0.05)。结论 二术天麻颗粒可显著降低PHT痰湿证大鼠血压、体重、Lee’s指数及一般状况评分,有效改善痰湿证表现,安全性良好,且高剂量效果更佳,可能与其纠正血脂异常、抗炎、抗氧化应激、增加NO含量、减少TMAO生成、改善主动脉病理损害有关。
Objective To investigate the effect of Erzhu Tianma granules(EZTM)on model rats with prehypertension(PHT)phlegm-dampness syndrome.Methods WKY rats were randomly divided into the control group,model group and EZTM high(1944 mg·kg^(-1)·d^(-1)),medium(972 mg·kg^(-1)·d^(-1))and low(486 mg·kg^(-1)·d^(-1))dose groups.A high-salt and high-fat diet was used to induce PHT phlegm-dampness syndrome in the model and EZTM rats.Different doses of EZTM were used as a six-week intervention.The activity,mental state,fecal character and other syndrome indexes were observed,and the general condition score was recorded.The body weight,Lee’s index and blood pressure(SBP,DBP,MAP)were measured.Blood was collected from the abdominal aorta,and blood lipid(TC,TG,HDL-C,LDL-C),inflammatory factors(CRP,TNF-α,IL-1β,IL-6),oxidative stress index(SOD,MDA),vasorelaxation factor(NO),TMAO levels,safety indexes(GLU,ALT,AST,Cr,BUN)were detected.The thoracic aorta was extracted and observed via HE and Masson staining.Results Compared with the control group,the model group showed symptoms of phlegm-dampness syndrome,such as lethargy,laziness,lack of energy and loose stool.The scores of general conditions,body weight,Lee’s index and blood pressure were increased(P<0.01),BP was maintained at 130-140/75-80 mmHg,TC,TG and LDL-C were increased(P<0.01),HDL-C was decreased(P<0.01),CRP,TNF-αand IL-1βwere increased(P<0.01),SOD activity was decreased(P<0.01),MDA was increased(P<0.01),NO was decreased(P<0.01),and TMAO was increased(P<0.01).The intima of the thoracic aorta was irregular,a small number of inflammatory cells were infiltrated,the thickness of the media thickened,the arrangement of smooth muscle cells was disorderly,and the collagen fibers increased significantly.Compared with the model group,the phlegm-dampness syndrome of rats in EZTM high and medium dose groups was improved.The score of general conditions,body weight,Lee’s index and blood pressure decreased(P<0.01),TC,TG,LDL-C decreased(P<0.01),HDL-C increased(P<0.01),CRP,TNF-α,IL-1βdecreased(P<0.01),SOD activity increased(P<0.01),MDA decreased(P<0.01),NO increased(P<0.01),and TMAO decreased(P<0.01).The intima of the thoracic aorta was smooth,no obvious inflammatory infiltration was observed,the thickness of the media was moderate,smooth muscle cells were arranged neatly,and the collagen fibers were reduced.The effect of high-dose EZTM was more pronounced.There were no significant differences in safety indexes between these groups(P>0.05).Conclusion Erzhu Tianma granules can effectively reduce blood pressure,body weight,Lee’s index and general condition scores,and improve the manifestations of phlegm-dampness syndrome,especially at a high dose.The mechanism may be related to correcting dyslipidemia,anti-inflammation,antioxidant stress,increasing NO contents,reducing TMAO production,and improving the pathological structural changes of the aorta.
作者
周思敏
林建国
王擎擎
姚魁武
ZHOU Simin;LIN Jianguo;WANG Qingqing;YAO Kuiwu(Department of Cardiology,Guang’anmen Hospital,China Academy of Chinese Medical Sciences,Beijing 100053,China;Internal Medicine Department,Eye Hospital,China Academy of Chinese Medical Sciences,Beijing 100040,China)
出处
《中国药物警戒》
2024年第9期998-1007,共10页
Chinese Journal of Pharmacovigilance
基金
国家自然科学基金资助项目(81873173)
国家重点研发计划(2019YFC1708703)
中国中医科学院科技创新工程重大攻关项目(CI2021A00906)
中国中医科学院科技创新工程创新团队(CI2021B004)
《临界性高血压中医诊疗指南》(No.T/CACM 1419-2022)。
