ABSTRACT
Objective To observe the effect of catgut implantation at acupoint(CIAA)on the learning and memory function,hippocampal microangiogenesis,and the mRNA and protein expression of angiopoietin-1(Ang-1)/vascular endothelialgrowth factor(VEGF)and its receptor TEK tyrosine kinase(TIE2)/VEGF receptor 2(VEGFR2)in rats with vascular dementia(VD).To explore the mechanism of catgut implantation at acupoint in preventing and treating VD.Methods Using a random number table,VD rats were divided into a model group,a nimodipine group,and an catgut implantation at acupoint group,and a sham operation group was set up,with 10 rats in each group.On the 7th day after surgery,the treatment groups were given catgut implantation at acupoint and nimodipine gastric lavage for 21 days.After treatment,Morris water maze behavioral test was performed.HE staining was used to observe hippocampal CA1 tissue.CD34 immunohistochemical staining was used to detect hippocampal microvascular density(MVD).Real-time PCR and Western blotting were used to detect the mRNA and protein expression of Ang-1/VEGF and its receptor TIE2/VEGFR2 in the hippocampus.Results Compared with the model group,the average escape latency of the other groups was significantly shortened,and the target quadrant residence time was significantly prolonged(P<0.01,P<0.05).Compared with the model group,the number of nucleolus and well-formed pyramidal cells in hippocampal CA1 area of the catgut implantation at acupoint group and the nimodipine group increased in varying degrees,and they were arranged more closely,with only a few cells scattered and swollen.In the sham surgery group,a few CD34 positive cells were scattered.The treatment groups had more closely distributed CD34 positive cells with significant staining compared to the model group.The MVD of the model group was significantly higher than that of the sham surgery group(P<0.01).Both nimodipine group and catgut implantation at acupoint group had higher MVD than the model group(P<0.05,P<0.01).Compared with the sham surgery group,the mRNA and protein expression of Ang-1/VEGF and its receptor TIE2/VEGFR2 in the model group increased significantly(P<0.01,P<0.05).Compared with the model group,both nimodipine group and catgut implantation at acupoint group had higher mRNA and protein expression of Ang-1/VEGF and its receptor TIE2/VEGFR2(P<0.01,P<0.05).Conclusion Catgut implantation at acupoint can improve the learning and memory abilities in VD rats,promote hippocampal microvascular angiogenesis,which may be related to the up-regulation of Ang-1/VEGF and its receptor TIE2/VEGFR2 mRNA and protein expression.
ABSTRACT
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.
Subject(s)
Animals , Rats , Dementia, Vascular/therapy , Electroacupuncture , Hippocampus/metabolism , Immunity , Myeloid Differentiation Factor 88 , Rats, Sprague-Dawley , Signal Transduction , Toll-Like Receptor 4/metabolismABSTRACT
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.