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自噬抑制剂氯喹对大鼠肾脏草酸钙晶体形成的作用及机制研究
  • ISSN号:1000-6702
  • 期刊名称:《中华泌尿外科杂志》
  • 时间:0
  • 分类:R287.32[医药卫生—中药学;医药卫生—中医学]
  • 作者机构:广州医科大学附属第一医院微创外科中心泌尿外科广东省泌尿外科重点实验室,510230
  • 相关基金:基金项目:国家自然科学基金(81370804,81670643,81570633)
中文摘要:

目的探讨自噬抑制剂氯喹对大鼠肾脏草酸钙晶体形成的影响及可能机制。 方法2016年9月至2016年10月将30只SPF级健康雄性SD大鼠按随机数字表法分为对照组、模型组和干预组,每组10只。对照组大鼠自由饮用灭菌水。模型组应用乙二醇和氯化铵诱导法建立大鼠肾脏草酸钙结石模型。干预组在造模的基础上,予腹腔注射氯喹40 mg/(kg·d)。造模28 d后收集各组大鼠24 h尿液和肾脏,应用偏光显微镜检测肾脏草酸钙晶体数量,应用透射电镜检测肾脏的自噬小体数量,应用全自动生化仪及离子色谱仪检测尿液中钙、镁、草酸及枸橼酸的含量,通过免疫组化染色法检测肾脏自噬标志物LC3、P62以及肾损伤标志物SOD、MCP-1及8-OHdG的表达情况,并采用RT-PCR检测肾脏草酸转运体SLC26A6的表达变化。 结果与模型组相比,干预组大鼠肾脏草酸钙晶体数量明显减少[(32.37±5.14)个/HP与(4.18±0.25)个/HP,P〈0.05]。与对照组相比,模型组肾脏自噬水平明显升高;而与模型组相比,干预组肾脏自噬水平则明显降低。对照组、模型组、干预组的尿草酸排泄量分别为:(3.1±1.5)、(22.5±8.1)、(2.8±1.2)mmol,尿枸橼酸排泄量分别为:(63.4±7.4)、(45.9±9.5)、(15.6±8.2)mmol;与对照组相比,模型组的尿草酸明显增高(P〈0.05),干预组的尿枸橼酸明显降低(P〈0.05);与模型组相比,干预组的尿草酸和尿枸橼酸均明显减低(P〈0.05)。对照组、模型组和干预组肾脏的SOD表达量分别为:42.24±4.16、19.21±2.25、39.08±3.53;MCP-1表达量分别为:4.02±0.51、8.45±0.55、5.52±0.34;8-OHdG表达量分别为:7.16±0.54、11.21±1.12、8.67±0.34。与对照组相比,模型组的SOD表达量明显降低(P〈0.05),MCP-1和8-OHdG表达量明显升高(P〈0.05)。与模型组相比,干预组的SOD表达量明显升高(P〈0.0

英文摘要:

ObjectiveTo investigate the effect and potential mechanism of autophagy inhibitor chloroquine on the calcium oxalate crystals formation in rats. MethodsFrom September 2016 to October 2016, Thirty healthy male SD rats were randomly divided into 3 groups: control group, model group and chloroquine intervention group. The method to establish calcium oxalate stone model was drinking water with 1% ethylene and 1% ammonium chloride freely. The rats of chloroquine intervention group were treat with chloroquine (40mg/kg·d) by intraperitoneal injection. Modeling was finished after 28 days. The amounts of renal calcium oxalate crystals were detected by polarizing microscope. For all groups, the amounts of autophagosome were detected by transmission electron microscope. Twenty four hour urine compositions for stone risk factors were detected. The expressions of oxidative stress injury related molecular markers (SOD, MCP-1 and 8-OHdG)and the expressions of autophagy markers (LC3 and P62) were detected by immunohistochemistry. The RNA expressions of SLC26A6 in kidney were detected by Real-time PCR. ResultsCompared to the model group, the amounts of renal calcium oxalate crystals were significantly reduced in chloroquine intervention group(32.37±5.14 vs. 4.18±0.25, P〈0.05). Compared to the control group, the level of autophagy was increased in the model group. Compared to the model group, the level of autophagy was inhibited in the chloroquine intervention group. For control group, model group and chloroquine intervention group, the excretion of urinary oxalate were (3.1±1.5)mmol, (22.5±8.1)mmol, (2.8±1.2)mmol, respectively; the excretion of urinary citrate were (63.4±7.4)mmol, (45.9±9.5)mmol, (15.6±8.2)mmol, respectively. Compared to the control group, the amounts of urinary oxalate were significantly elevated in model group(P〈0.05), but citrate were significantly reduced in the chloroquine intervention group(P〈0.05). For control group, model group and chl

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期刊信息
  • 《中华泌尿外科杂志》
  • 中国科技核心期刊
  • 主管单位:中国科学技术协会
  • 主办单位:中华医学会
  • 主编:
  • 地址:北京东单三条甲七号
  • 邮编:100005
  • 邮箱:mnzz@263.net.cn
  • 电话:010-65223499
  • 国际标准刊号:ISSN:1000-6702
  • 国内统一刊号:ISSN:11-2330/R
  • 邮发代号:2-51
  • 获奖情况:
  • 国家期刊提名奖,中国科协优秀科技期刊
  • 国内外数据库收录:
  • 美国化学文摘(网络版),日本日本科学技术振兴机构数据库,中国中国科技核心期刊,中国北大核心期刊(2004版),中国北大核心期刊(2008版),中国北大核心期刊(2011版),中国北大核心期刊(2014版),中国北大核心期刊(2000版)
  • 被引量:42676