滋肾活血方对血管性痴呆大鼠认知功能障碍的治疗作用OACSTPCD

Objective To explore the molecular mechanism of Zishen Huoxue recipe alleviating cognitive impairment in rats with vas-cular dementia(VD).Methods A rat model of VD was established using the bilateral common carotid artery occlusion(BCCAO)method.Rats were randomized into sham group,VD group,high-dose Zishen Huoxue recipe(15.2 g/kg)group,medium-dose Zishen Huoxue recipe(7.6 g/kg)group,low-dose Zishen Huoxue recipe(3.8 g/kg)group,and Oxiracetam group(positive control).The escape latency and the number of platform crossings were tested by the Morris water maze test to assess the cognitive function of rats.Pathological changes and inflammatory cell infiltration in hippocampal tissues were observed by HE staining.Hippocampal neuron injury was evaluated by Nissl staining.The M1/M2 polarization of microglia in hippocampal tissues was detected by immunofluorescence.In hippocampal tissues,the levels of pro-inflammatory factors(TNF-α and IL-1β)and anti-inflammatory factors(TGF-β and 1L-4)were measured by ELISA,and the protein levels of TLR4 and nuclear p65 were measured by Western blot.Results Compared with sham group,the escape latency was increased while the number of crossing the platform was decreased in VD group(P＜0.001),the hippo-campal neurons were irregularly arranged and the inflammatory cell infiltration was increased,and the levels of Iba-1,CD16/32,CD206,TNF-α,IL-1β,TGF-β,IL-4,TLR4,and nuclear p65 were increased(P＜0.001).Compared with VD group,the escape latency was shortened(P＜0.05),while the number of crossing the platform was increased in in high-,medium-,low-dose Zishen Huoxue recipe groups and Oxiracetam group(P＜0.01),the pathological changes of hippocampal neuron were improved,the levels of Iba-1,CD16/32,CD206,TNF-α,IL-1β,TLR4,and nuclear p65 were diminished(P＜0.01),and the levels of TGF-β and IL-4 were upregulated(P＜0.01).Conclusion Zishen Huoxue recipe can ameliorate the cognitive impairment in VD rats by facilitating the polarization of microglia from M1 to M2 via the inhibition of TLR4/NF-κB pathway.