Electroacupuncture Attenuates Immune-Inflammatory Response in Hippocampus of Rats with Vascular Dementia by Inhibiting TLR4/MyD88 Signaling Pathway / 中国结合医学杂志

OBJECTIVE@#To investigate whether electroacupuncture (EA) alleviates cognitive impairment by suppressing the toll-like receptor 4 (TLR4)/myeloid differentiation factor 88 (MyD88) signaling pathway, which triggers immune-inflammatory responses in the hippocampus of rats with vascular dementia (VaD).@*METHODS@#The experiments were conducted in 3 parts and in total the Sprague-Dawley rats were randomly divided into 8 groups by a random number table, including sham, four-vessel occlusion (4-VO), 4-VO+EA, 4-VO+non-EA, sham+EA, 4-VO+lipopolysaccharide (LPS), 4-VO+LPS+EA, and 4-VO+TAK-242 groups. The VaD model was established by the 4-VO method. Seven days later, rats were treated with EA at 5 acupoints of Baihui (DV 20), Danzhong (RN 17), Geshu (BL 17), Qihai (RN 6) and Sanyinjiao (SP 6), once per day for 3 consecutive weeks. Lymphocyte subsets, lymphocyte transformation rates, and inflammatory cytokines interleukin-6 (IL-6) and tumor necrosis factor α(TNF-α) were measured to assess immune function and inflammation in VaD rats. Transmission electron microscopy was used to observe the ultrastructure of nerve cells in the hippocampus. The levels of TLR4, MyD88, IL-6, and TNF-α were detected after EA treatment. TLR4/MyD88 signaling and cognitive function were also assessed after intracerebroventricular injection of TLR4 antagonist TAK-242 or TLR4 agonist LPS with or without EA.@*RESULTS@#Compared with the 4-VO group, EA notably improved immune function of rats in the 4-VO+EA group, inhibited the protein and mRNA expressions of TLR4 and MyD88 in the hippocampus of rats, reduced the expressions of serum IL-6 and TNF-α (all P0.05).@*CONCLUSIONS@#EA attenuated cognitive impairment associated with immune inflammation by inhibition of the TLR4/MyD88 signaling pathway. Thus, EA may be a promising alternative therapy for the treatment of VaD.

Acupoint catgut embedding inhibiting neuroinflammation in vascular dementia rats / 解剖学报

Objective To observe the effect of acupoint catgut embedding on the expression of inflammatory factor mRNA in cyclooxygenase-2 (COX-2)/prostaglandin E2 (PGE2) signal pathway of vascular dementia (VD) rats, and to explore the protective mechanism of acupoint catgut embedding on the brain inflammatory response of VD rats. Methods VD model was established by the modified Pulsinelli ' s four vessel blocking method. Totally 148 male rats were randomly divided into VD model group, non acupoint catgut embedding group and acupoint catgut embedding group. On the 7th day after operation, catgut embedding at acupoints and catgut embedding at non acupoints were performed in the two treatment groups respectively, and materials were taken out 15 days later. Western blotting was used to detect the expression of COX-2 and PGE2, and real-time PCR was used to detect the mRNA expression of tumor necrosis factor α (TNF-α), intercellular cell adhesion molecule 1 (ICAM-1), interieukin(IL)-6, macrophage inflammatory protein 2 (MIP-2), IL-lβ, and monocyte chemotactic protein 1 ( MCP-1 ) in rat hippocampus. Results Compared with the sham group, the expressions of COX-2, PGE2, TNF-α, ICAM-1, IL-6, MIP-2, IL-lβ and MCP-1 in hippocampus of the other three groups were significantly higher (P<0.01). Compared with the model group, the expressions of COX-2, PGE2 protein and TNF-α, ICAM-1, IL-6, MIP-2, IL-lβ, MCP-1 mRNA in the hippocampus of the acupoint catgut embedding group and the non acupoint catgut embedding group decreased significantly (P<0.01). Conclusion Acupoint catgut embedding can protect the brain from inflammatory injury by down-regulating the expression of related inflammatory factors in COX-2/PGE2 signaling pathway and reducing the inflammatory response induced by VD rats.