Study on Mechanism of Zuogui Jiangtang Jieyu Prescription in Modulating Dopamine Receptors to Ameliorate Neuroinflammation in Rats of Diabetes Mellitus Complicated with Depression
10.19879/j.cnki.1005-5304.202404290
- VernacularTitle:左归降糖解郁方调控多巴胺受体改善糖尿病并发抑郁症大鼠神经炎症的作用机制研究
- Author:
Ping LI
1
;
Manshu ZOU
;
Tingting WANG
;
Haipeng GUO
;
Tingting REN
;
Yingxi LIU
;
Yingjuan TANG
;
Ying HE
;
Yuhong WANG
;
Yuanshan HAN
Author Information
1. 湖南中医药大学科技创新中心,湖南 长沙 410208
- Keywords:
Zuogui Jiangtang Jieyu Prescription;
diabetes mellitus complicated with depression;
dopamine receptor;
NLRP3;
neuroinflammation
- From:
Chinese Journal of Information on Traditional Chinese Medicine
2024;31(12):112-119
- CountryChina
- Language:Chinese
-
Abstract:
Objective To explore the effect and related mechanism of Zuogui Jiangtang Jieyu Prescription on neuroinflammation of nucleus accumbens in rats with diabetes mellitus(DM)complicated with depression based on dopamine receptor.Methods DM,depression and DM complicated with depression models were respectively established through a combination of high-fat feeding and streptozotocin intraperitoneal injection,as well as chronic unpredictable mild stress+solitary cage feeding.The rats were divided into control group,depression group,DM group,DM complicated with depression group,positive group,D1R agonists group,D2/3R agonists group and Zuogui Jiangtang Jieyu Prescription group.Depression and learning and memory abilities in rats were assessed using open field experiments,forced swimming experiments and water maze experiments.Neuronal damage in nucleus accumbens was detected through HE and Nissl staining.Serum contents of 5-hydroxytryptamine(5-HT),dopamine(DA),interleukin(IL)-1β and IL-18 were detected by ELISA.The expressions of D1R,D2R,D3R and Iba1/NLRP3 in nucleus accumbens were detected by immunofluorescence.The protein expressions of D1R,D2R,D3R,NLRP3,ASC,Caspase-1 p20 and IL-1β in nucleus accumbens were detected by Western blot.Results Compared with the control group,the changes of fasting blood glucose(FBG)in rats of DM complicated with depression group significantly increased(P<0.01),the total distance and number of activities in the open field experiment,the time ratio of staying in the original platform quadrant and the number of times crossed the original platform in the water maze experiment significantly decreased(P<0.05,P<0.01),the forced swimming immobility time and the escape latency period in the water maze experiment were prolonged(P<0.05,P<0.01),the contents of serum 5-HT and DA significantly decreased(P<0.01),the contents of IL-1β and IL-18 significantly increased(P<0.05,P<0.01),neurons in the nucleus accumbens showed nuclear condensation,degeneration,and increased necrotic cells,with loss of Nissl bodies,the expressions of D1R,D2R and D3R were significantly decreased(P<0.01),while the expressions of NLRP3,ASC,Caspase-1 p20 and IL-1β protein significantly increased(P<0.05,P<0.01).Compared with the DM complicated with depression group,the changes of FBG significantly decreased in the Zuogui Jiangtang Jieyu Prescription group,learning and memory abilities were enhanced,depression-like behavior was improved,and the damage to neurons in the nucleus accumbens was reduced,the contents of serum 5-HT and DA significantly increased(P<0.01),the contents of IL-1β and IL-18 significantly decreased(P<0.01),the expressions of D1R,D2R and D3R in the nucleus accumbens increased(P<0.05,P<0.01),and the expressions of NLRP3,ASC,Caspase-1 p20 and IL-1β protein decreased(P<0.05,P<0.01).Conclusion The dopaminergic system dysfunction and neuroinflammation are the key mechanisms of DM complicated with depression.Zuogui Jiangtang Jieyu Prescription may improve neuroinflammation by regulating the dopamine receptor to inhibit the activation of microglial NLRP3 signaling in the nucleus accumbens.
