穿心莲内酯对脑梗死合并细菌性肺炎大鼠模型肺组织炎症和神经功能的影响  

Effects of andrographolide on inflammation and neurological function in a rat model of bacterial pneumonia combined with cerebral infarction

作　　者：盘爱花 邝小玲 陈永敏[1] 陈家凤 谭春苗 PAN Ai-hua;KUANG Xiao-ling;CHEN Yong-min;CHEN Jia-feng;TAN Chun-miao(The First Affiliated Hospital of Hainan Medical University,Haikou,Hainan 570102,China)

机构地区：[1]海南医学院第一附属医院神经内科二病区,海南海口570102 [2]海南医学院第一附属医院呼吸内科,海南海口570102

出　　处：《中华医院感染学杂志》2021年第7期961-966,共6页Chinese Journal of Nosocomiology

基　　金：海南省卫生计生行业科研基金资助项目(18A200120)。

摘　　要：目的探索穿心莲内酯(ANG)对脑梗死(CI)合并细菌性肺炎(BP)大鼠模型肺组织炎症和神经功能的影响。方法将60只SD大鼠随机分为对照组、模型组和穿心莲内酯高、中、低剂量组(250、125、62.5 mg/kg,连续灌胃14 d)各12只。除对照组外所有大鼠均采用改良线栓法联合气管注射法制备CI合并BP模型。ANG连续灌胃14 d后,Longa评分法评估神经功能缺损评分,氯化三苯基四氮唑(TTC)法检测脑梗死灶体积百分比,原位末端标记法(TUNEL)检测脑组织细胞凋亡率,酶联免疫吸附法(ELISA)检测血清和肺组织中肿瘤坏死因子α(TNF-α)、白介素(IL)-6和IL-1β水平,Western blot检测肺组织中Toll样受体4(TLR4)、核转录因子κB(NF-κB) p65、p-NF-κB p65、裂解的半胱天冬酶3(cleaved Caspase-3)表达;HE染色观察脑组织和肺组织病理变化。结果与对照组相比,模型组和穿心莲内酯低剂量组大鼠神经元细胞凋亡率升高(P<0.05),血清和肺组织中TNF-α、IL-6、IL-1β水平升高(P<0.05),肺组织TLR4、p-NF-κB p65/NF-κB p65和cleaved Caspase-3水平升高(P<0.05);与模型组相比,穿心莲内酯高、中剂量组大鼠神经功能缺损评分下降[(2.42±0.48)分、(2.76±0.50)分vs (3.32±0.51)分,P<0.05],脑梗死体积百分比缩小[(24.76±5.33)%、(28.53±5.24)%vs (33.28±5.82)%,P<0.05],神经元细胞凋亡率下降[(15.32±3.90)%、(19.36±4.87)%vs (27.65±5.84)%,P<0.05],血清和肺组织中TNF-α、IL-6、IL-1β水平下降(P<0.05),肺组织TLR4、p-NF-κB p65/NF-κB p65和cleaved Caspase-3水平下降(P<0.05),HE染色显示脑组织和肺组织损伤减轻。结论 ANG可能通过抑制CI合并BP大鼠肺组织TLR4/NF-κB信号通路,降低机体的炎症因子水平,减轻脑组织和肺组织损伤。OBJECTIVE To explore the effect of andrographolide(ANG) on inflammation and neurological function in pulmonary tissues of a rat model of bacterial pneumonia(BP) complicated with cerebral infarction(CI). METHODS Sixty SD rats were randomly divided into the control group, model group and three ANG groups, including high-dose(250 mg/kg), medium-dose(125 mg/kg) and low-dose(62.5 mg/kg) ANG groups, which were given continuous intragastric administration for 14 d. Twelve cases were included in each group. Except for the control group, the rat model of CI combined BP in all other groups were prepared by using modified thread-occlusion method and tracheal injection method. After 14 days of continuous ANG intragastric administration, neurological deficits were scored by Longa scoring method. The percentage of cerebral infarct volume was detected by triphenyltetrazolium chloride(TTC). The apoptosis rate of brain tissues was detected by TdT-mediated biotinylated-dUTP nick end labeling(TUNEL). The levels of tumor necrosis factor α(TNF-α), interleukin(IL)-6 and IL-1β in serum and pulmonary tissues were detected by enzyme linked immunosorbent assay(ELISA). The expression of Toll-like receptor 4(TLR4), nuclear transcription factor κB(NF-κB), p65, P-NF-κB p65 and cleaved caspase-3 in pulmonary tissues was detected by Western blot. The pathological changes of brain tissues and pulmonary tissues were observed by HE staining. RESULTS Compared with the control group, apoptosis rate of neurons was significantly increased in the model group and low-dose ANG group(P<0.05);levels of TNF-α, IL-6 and IL-1β in serum and pulmonary tissues were significantly increased(P<0.05);levels of TLR4, p-NF-κB p65/NF-κB p65 and cleaved Caspase-3 in pulmonary tissues were significantly increased(P<0.05). Compared with the model group, scores of neurological deficits were significantly decreased in the high-dose and medium-dose ANG groups(3.32±0.51 vs 2.42±0.48 and 2.76±0.50, P<0.05];percentage of cerebral infarction volume was significantly

关 键 词：脑梗死 细菌性肺炎 穿心莲内酯 炎症 神经功能 

分 类 号：R563.1[医药卫生—呼吸系统]