鲜地黄及其多糖对实热大鼠焦虑模型影响的研究

Effect of Fresh Dihuang(地黄)and Its Polysaccharide on Anxiety Model in Rats with Shire(实热)Syndrome

目的:观察鲜地黄及其多糖对实热大鼠焦虑模型的抗焦虑药效,并探讨其作用机制。方法:将110只SD大鼠随机分成正常对照组、焦虑模型对照组、实热焦虑模型对照组、地西泮2.0 mg/kg组,鲜地黄水煎液1.5、3、6 g/kg组、鲜地黄多糖0.3、0.6、1.2 g/kg组、鲜地黄非多糖0.6 g/kg组。正常对照组大鼠正常喂养,焦虑模型对照组大鼠于末次给药后进行装置焦虑造模,其余各组大鼠灌胃党参-黄芪水煎液14 d,造模成功后各组ig相应药物,连续5 d。联合高架十字迷宫(EPM)、明暗箱装置制备实热大鼠焦虑复合模型。观察大鼠一般形态、饮水量及肛温的变化,评价大鼠的焦虑行为;ELISA法检测大鼠脑组织中γ-氨基丁酸(GABA)、谷氨酸(Glu)、5-羟色胺(5-HT)和多巴胺(DA)含量,血清中三碘甲状腺原氨酸(T_(3))、甲状腺素(T_(4))、促甲状腺激素(TSH)、反三碘甲状腺原氨酸(rT_(3))含量,血浆中促肾上腺皮质激素(ACTH)、皮质酮(CORT)含量及肝组织中琥珀酸脱氢酶(SDH)的含量。结果:与正常对照组比较,焦虑模型对照组大鼠体内5-HT、SDH含量明显升高(P<0.05或P<0.01),DA、rT_(3)含量明显降低(P<0.05或P<0.01);与焦虑模型对照组比较,实热焦虑模型对照组大鼠饮水量增多、肛温升高,体内5-HT、T_(4)、TSH、ACTH、CORT、SDH含量明显升高(P<0.05),大鼠行为学试验中开臂进入次数百分比(OE%)和开臂滞留时间百分比(OT%)、GABA、DA、rT_(3)含量明显降低(P<0.05);与实热焦虑模型对照组比较,鲜地黄及其多糖可改善大鼠实热证的症状,显著提高OE%、OT%及明暗箱穿梭次数,及GABA、DA、rT_(3)的含量(P<0.05或P<0.01),显著降低Glu、5-HT、T_(3)、T_(4)、TSH、ACTH、CORT、SDH的含量(P<0.05或P<0.01)。结论:鲜地黄及其多糖对实热大鼠焦虑模型具有一定的抗焦虑作用,其作用机制与升高脑组织中GABA和DA的含量、降低Glu和5-HT的含量,以及抑制下丘脑-垂体-甲状腺(HPT)轴和下丘脑-垂体-肾上腺(HPA)轴功能亢进等途径有关。

Objective:To observe the anti anxiety effect of fresh Dihuang and its polysaccharide on the anxiety model in rats with Shire syndrome,and explore its mechanism.Methods:A total of 110 SD rats were randomly divided into a normal control group,an anxiety model group,an anxiety model with Shire syndrome group,a diazepam group(2.0 mg/kg),fresh Dihuang decoction groups(6 g/kg,3 g/kg,and 1.5 g/kg),fresh Dihuang polysaccharide groups(1.2 g/kg,0.6 g/kg,and 0.3 g/kg),and a fresh Dihuang non-polysaccharide group(0.6 g/kg).Rats in the normal control group were fed on a normal diet,and those in the anxiety model group underwent anxiety modeling after the last administration,while those in other groups received Dangshen(党参)-Huangqi(黄芪)decoction by gavage for 14 days.After modeling,all rats were administered with corresponding drugs for five days.The anxiety model with Shire symptom in rats was induced by elevated plus maze(EPM)combined with light/dark box.The general conditions,water intake,and anal temperature of rats were observed,and the anxiety-like behaviors of rats were evaluated.The content ofγ-aminobutyric acid(GABA),glutamic acid(Glu),5-hydroxytryptamine(5-HT),and dopamine(DA)in brain tissues,triiodothyronine(T_(3)),thyroxine(T_(4)),thyroid-stimulating hormone(TSH),and reverse triiodothyronine(rT_(3))in the serum,adrenocorticotrophic hormone(ACTH)and corticosterone(CORT)in the plasma,and succinate dehydrogenase(SDH)in liver tissues were measured by enzyme-linked immunosorbent assay(ELISA).Results:Compared with the normal control group,the anxiety model group showed increased 5-HT and SDH(P<0.05 or P<0.01)and decreased content of DA and rT_(3)(P<0.05 or P<0.01).Compared with the anxiety model group,the anxiety model with Shire syndrome group showed increased water intake and anal temperature,elevated content of 5-HT,T_(4),TSH,ACTH,CORT,and SDH(P<0.05),decreased percentages of open arm entries(OE%)and open arm time(OT%),and reduced content of GABA,DA,and rT_(3)(P<0.05).Compared with the conditions in the anxiety model with Shire syndrome group,fresh Dihuang and polysaccharide could improve Shire syndrome,increased OE%,OT%,and the number of crossings in the light/dark box,up-regulated the content of GABA,DA,and rT_(3)(P<0.05 or P<0.01),and reduced the content of Glu,5-HT,T_(3),T_(4),TSH,ACTH,CORT,and SDH(P<0.05 or P<0.01).Conclusion:Fresh Dihuang and its polysaccharide possess a certain anti anxiety effect on the anxiety model in rats with Shire syndrome.The mechanism of action is related to the increase in the content of GABA and DA in brain tissues,the reduction of the content of Glu and 5-HT,and the inhibition of the hyperfunction of the hypothalamic pituitary thyroid(HPT)axis and the hypothalamic pituitary adrenal(HPA)axis.