间歇高CO2对睡眠呼吸暂停早期肾损伤及HMGB1信号通路表达的影响  

Effect of intermittent high CO2 on early renal injury and expressions of HMGB1 signaling pathway

作　　者：张成[1] 马靖[1] 陈凤惟 王凯乐 吴松杰 马元元[2] 张珏 王广发[1] Zhang Cheng;Ma Jing;Chen Fengwei;Wang Kaile;Wu Songjie;Ma Yuanyuan;Zhang Jue;Wang Guangfa(Guangfa Department of Resp iratory and Critical Care Medicine ,Peking University First Hospital , Beijing 100034,China)

机构地区：[1]北京大学第一医院呼吸和危重症医学科,100034 [2]北京大学第一医院实验动物中心,100034 [3]北京大学前沿交叉学科研究院,100034 [4]北京大学工学院,100034

出　　处：《国际呼吸杂志》2018年第23期1775-1781,共7页International Journal of Respiration

基　　金：国家自然科学基金(81341005)。

摘　　要：目的探讨间歇高CO2在睡眠呼吸暂停早期肾损伤中的作用及其分子机制。方法建立单纯间歇高CO2、间歇低氧伴高CO2的大鼠模型,每组10只,分别持续2周。并设立正常对照组(n=10)。留取外周血标本和肾脏标本。应用石蜡切片HE染色以及透射电镜的方法,观察肾脏病理和超微结构。应用real‐timePCR的方法检测HMGB1‐TLR4‐NF‐κB‐TNF‐α/IL‐6通路mRNA的表达。结果(1)HE染色光镜观察:单纯间歇高CO2组和间歇低氧伴高CO2组大鼠均无显著病理损伤,但可见一定程度的肾小管上皮空泡变性,单纯间歇高CO2组的损伤程度轻于间歇低氧伴高CO2组;(2)电镜观察超微结构:单纯间歇高CO2和间歇低氧伴高CO2均可致部分肾小球足突融合、溶酶体增多。单纯间歇高CO2足突融合程度较间歇低氧伴高CO2组轻;(3)与正常对照组相比,单纯间歇高CO2组中HMGB1、IL‐6mRNA的表达显著升高(P<0.05),间歇低氧伴高CO2组大鼠HMGB1、PPAR和TNF‐αmRNA的表达显著升高(P<0.05)。与间歇低氧伴高CO2组相比,多数HMGB1信号通路的因子在单纯间歇高CO2组的表达均呈下降的趋势,但两组比较差异无统计学意义(P>0.05)。结论单纯间歇高CO2可能通过HMGB1通路造成早期肾损伤,其损伤程度略轻于间歇低氧伴高CO2组。在睡眠呼吸暂停相关的早期肾损伤中,单纯间歇高CO2可能仍为一损伤因素而非保护性因素。Objective To investigate the role of intermittent high CO2 in early renal injury and its molecular mechanisms .Methods Simple intermittent high CO2 and intermittent hypoxia with high CO2 rat models were established ,which lasted for two weeks respectively ( n = 10 ) .Peripheral blood and kidney samples were retained .The pathological and ultrastructure of the kidney were observed by HE staining and the method of scanning electron microscope .The expressions of HMGB1‐TLR4‐NF‐κB‐TNF‐ α/IL‐6 pathway were detected by the method of real‐time PCR .Results ( 1 ) HE staining and light microscope observations :intermittent hypoxia with high CO2 group and simple intermittent high CO2 group both showed mild renal tubular epithelial vacuolar degeneration ,and the injury degree in simple intermittent high CO2 group was slighter than that in intermittent hypoxia with high CO2 group .(2) The ultrastructures observed by transmission electron microscope :foot process fusion in the glomerulus and increased lysosomes in renal tubular epithelial cell were seen in both intermittent hypoxia with high CO 2 and simple intermittent high CO2 groups . ( 3 ) Compared to the normal control group , the mRNAexpressions of HMGB1 ,PPAR and TNF alpha were significantly increased ( P < 0 .05 ) in intermittent hypoxia with high CO2 group .And the mRNA expressions of HMGB1 ,IL‐6 in simple intermittent high CO2 group significantly increased ( P < 0 .05 ) .Compared with the intermittent hypoxia and high CO 2 group ,the expression of most factors in HMGB1 signaling pathway had the trend of descending in the simple intermittent high CO2 group ,however there were no significant differences between two groups ( P > 0 .05 ) .Conclusions Simple intermittent high CO2 is associated with early renal injury through HMGB1 pathway ,and the degree of injury is slightly less than that in intermittent hypoxia with high CO 2 group .This study failed to confirm the protective effect of CO 2 .The mechanism of CO2 in early renal injury associated with

关 键 词：低氧 高二氧化碳 阻塞性睡眠呼吸暂停 肾损伤 高迁移率蛋白1 

分 类 号：R56[医药卫生—呼吸系统]