PMID- 38114178 OWN - NLM STAT- MEDLINE DCOM- 20231221 LR - 20231221 IS - 1001-5302 (Print) IS - 1001-5302 (Linking) VI - 48 IP - 21 DP - 2023 Nov TI - [Neuroprotective effect and mechanism of Zuogui Jiangtang Jieyu Formula on diabetes mellitus complicated with depression model rats based on CX3CL1-CX3CR1 axis]. PG - 5822-5829 LID - 10.19540/j.cnki.cjcmm.20230605.406 [doi] AB - Based on the CX3C chemokine ligand 1(CX3CL1)-CX3C chemokine receptor 1(CX3CR1) axis, this study explored the potential mechanism by which Zuogui Jiangtang Jieyu Formula(ZGJTJY) improved neuroinflammation and enhanced neuroprotective effect in a rat model of diabetes mellitus complicated with depression(DD). The DD rat model was established by feeding a high-fat diet combined with streptozotocin(STZ) intraperitoneal injection for four weeks and chronic unpredictable mild stress(CUMS) combined with isolated cage rearing for five weeks. The rats were divided into a control group, a model group, a positive control group, an inhibitor group, and a ZGJTJY group. The open field test and forced swimming test were used to assess the depression-like behaviors of the rats. Enzyme-linked immunosorbent assay(ELISA) was performed to measure the expression levels of the pro-inflammatory cytokines interleukin-1beta(IL-1beta) and tumor necrosis factor-alpha(TNF-alpha) in plasma. Immunofluorescence staining was used to detect the expression of ionized calcium-binding adapter molecule 1(Iba1), postsynaptic density protein-95(PSD95), and synapsin-1(SYN1) in the hippocampus. Hematoxylin-eosin(HE) staining, Nissl staining, and TdT-mediated dUTP nick end labeling(TUNEL) fluorescence staining were performed to assess hippocampal neuronal damage. Western blot was used to measure the expression levels of CX3CL1, CX3CR1, A2A adenosine receptor(A2AR), glutamate receptor 2A(NR2A), glutamate receptor 2B(NR2B), and brain-derived neurotrophic factor(BDNF) in the hippocampus. Compared with the model group, the ZGJTJY group showed improved depression-like behaviors in DD rats, enhanced neuroprotective effect, increased expression of PSD95, SYN1, and BDNF(P<0.01), and decreased expression of Iba1, IL-1beta, and TNF-alpha(P<0.01), as well as the expression of CX3CL1, CX3CR1, A2AR, NR2A, and NR2B(P<0.01). These results suggest that ZGJTJY may exert its neuroprotective effect by inhibiting the CX3CL1-CX3CR1 axis and activation of hippocampal microglia, thereby improving neuroinflammation and abnormal activation of N-methyl-D-aspartate receptor(NMDAR) subunits, and ultimately enhancing the expression of synaptic-related proteins PSD95, SYN1, and BDNF in the hippocampus. FAU - Li, Ping AU - Li P AD - Technology Innovation Center,Hunan University of Chinese Medicine Changsha 410208,China. FAU - Liu, Yang AU - Liu Y AD - Technology Innovation Center,Hunan University of Chinese Medicine Changsha 410208,China. FAU - Zou, Man-Shu AU - Zou MS AD - Technology Innovation Center,Hunan University of Chinese Medicine Changsha 410208,China Hunan Provincial Key Laboratory of Prevention and Treatment of Depressive Diseases with Traditional Chinese Medicine Changsha 410208,China. FAU - Wang, Ting-Ting AU - Wang TT AD - Technology Innovation Center,Hunan University of Chinese Medicine Changsha 410208,China. FAU - Guo, Hai-Peng AU - Guo HP AD - Technology Innovation Center,Hunan University of Chinese Medicine Changsha 410208,China. FAU - Ren, Ting-Ting AU - Ren TT AD - Technology Innovation Center,Hunan University of Chinese Medicine Changsha 410208,China. FAU - He, Ying AU - He Y AD - Technology Innovation Center,Hunan University of Chinese Medicine Changsha 410208,China. FAU - Wang, Hua AU - Wang H AD - the First Affiliated Hospital of Hunan University of Chinese Medicine Changsha 410007,China. FAU - Wang, Yu-Hong AU - Wang YH AD - Technology Innovation Center,Hunan University of Chinese Medicine Changsha 410208,China Hunan Provincial Key Laboratory of Prevention and Treatment of Depressive Diseases with Traditional Chinese Medicine Changsha 410208,China. LA - chi PT - English Abstract PT - Journal Article PL - China TA - Zhongguo Zhong Yao Za Zhi JT - Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica JID - 8913656 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (zuogui) RN - 0 (Neuroprotective Agents) RN - 0 (Tumor Necrosis Factor-alpha) RN - 0 (Receptors, Glutamate) RN - 0 (CX3CR1 protein, rat) RN - 0 (CX3C Chemokine Receptor 1) SB - IM MH - Rats MH - Animals MH - Depression/drug therapy MH - Brain-Derived Neurotrophic Factor MH - *Neuroprotective Agents MH - Tumor Necrosis Factor-alpha/metabolism MH - Neuroinflammatory Diseases MH - *Diabetes Mellitus MH - Receptors, Glutamate MH - CX3C Chemokine Receptor 1/genetics OTO - NOTNLM OT - CX3C chemokine ligand 1(CX3CL1) OT - CX3C chemokine receptor 1(CX3CR1) OT - Zuogui Jiangtang Jieyu Formula OT - diabetes mellitus complicated with depression OT - synaptic proteins EDAT- 2023/12/20 06:41 MHDA- 2023/12/21 06:43 CRDT- 2023/12/19 20:44 PHST- 2023/12/21 06:43 [medline] PHST- 2023/12/20 06:41 [pubmed] PHST- 2023/12/19 20:44 [entrez] AID - 10.19540/j.cnki.cjcmm.20230605.406 [doi] PST - ppublish SO - Zhongguo Zhong Yao Za Zhi. 2023 Nov;48(21):5822-5829. doi: 10.19540/j.cnki.cjcmm.20230605.406.