STING-Caspase-1信号通路对创伤性颅脑损伤大鼠认知功能障碍的作用

Effect of STING-Caspase-1 signaling pathway on cognitive impairment induced by traumatic brain injury in rat models

目的探讨干扰素基因刺激蛋白(STING)-半胱天冬酶(Caspase-1)信号通路在颅脑创伤致大鼠认知功能障碍中的作用。方法将48只清洁级雄性SD大鼠随机分为4组,假手术组(S组)、模型组(M组)、STING抑制剂C-176组(C组)和STING激动剂ADU-s100组(A组)各12只。通过重物自由落体撞击硬脑膜法建立创伤性颅脑损伤(TBI)模型。M组、C组和A组大鼠建立TBI模型后,C组和A组分别经腹腔注射C-17610 mg/kg和ADU-s10010 mg/kg。S组只行骨瓣开窗术。建模后第7日行Morris水迷宫测试评估大鼠认知功能,然后处死大鼠取其海马组织,采用免疫荧光法测定STING/胶质纤维酸性蛋白(GFAP)、活化Caspase-1/Neuron表达情况。结果与S组比较,M组、C组和A组大鼠Morris水迷宫测试的潜伏期延长,穿越平台次数减少,目标象限停留时间缩短,STING/GFAP、活化Caspase-1/Neuron阳性率上调(P均<0.05)。与C组比较,M组、A组大鼠潜伏期延长,穿越平台次数减少,目标象限停留时间缩短,STING/GFAP、活化Caspase-1/Neuron阳性率上调(P均<0.05)。与A组比较,M组大鼠潜伏期缩短,穿越平台次数增加,目标象限停留时间延长,STING/GFAP、活化Caspase-1/Neuron阳性率G下调(P均<0.05)。结论STING-Caspase-1信号通路可能参与了TBI中认知功能障碍的病理生理过程。

Objective To explore the role of stimulator of interferon genes(STING)-Caspase-1 signaling pathway on cognitive impairment induced by traumatic brain injury(TBI)in rat models.Methods Forty-eight clean grade healthy male SD rats were randomly and evenly divided into the shamoperation group(S group),model group(M group),C-176 group(C group)and ADU-s100 group(A group).TBI rat models were established by using a weight-drop head injury method.After the establishment of TBI rat models,C-176(10 mg/kg)and ADU-s100(10 mg/kg)were injected intraperitoneally in the C and A groups.Bone flap fenestration alone was performed in the S group.At 7 d after the model was established,Morris water maze was performed to assess the cognitive ability of rats.Then,the rats were sacrificed and the hippocampus was taken.Immunofluorescent staining was used to determine the expression levels of STING/glial fibrillary acidic protein(GFAP)and cleaved-Caspase-1/Neuron.Results Compared with the S group,the latency was significantly prolonged,the number of passing the platform was remarkably reduced,the time of stay in the target quadrant was considerably shortened,and the positive rates of STING/GFAP and cleaved-Caspase-1/Neuron were significantly up-regulated in the M,C and A groups(all P<0.05).Compared with the C group,the latency was significantly prolonged,the number of passing the platform was remarkably reduced,the time of stay in the target quadrant was considerably shortened,and the positive rates of STING/GFAP and cleaved-Caspase-1/Neuron were significantly up-regulated in the M and A groups(all P<0.05).Compared with the A group,the latency was significantly shortened,the number of passing the platform was remarkably increased,the time of stay in the target quadrant was considerably prolonged,and the positive rates of STING/GFAP and cleaved-Caspase-1/Neuron were significantly down-regulated in the M group(all P<0.05).Conclusion STING-Caspase-1 signaling pathway is probably involved with the pathophysiological process of cognitive impairment induced by TBI in rat models.