硫酸镁通过Toll样受体4/核转录因子-κB通路抑制慢性肾衰竭大鼠血管钙化的机制研究  

Mechanism of magnesium sulfate suppressing vascular calcification in rats with chronic renal failure through TLR4/NF-κB pathway

作　　者：董丽明[1] 李寅辉[2] 米克热衣·艾孜买提[3] 李莉[1] Dong Li-ming;Li Yin-hui;Mike-Reyi·Aizimati;Li Li(Department of Clinical Nutrition,The First Affiliated Hospital of Xinjiang Medical University,Urumqi 830000,China;Department of Endocrinology,Affiliated Hospital of Traditional Chinese Medicine,Xinjiang Medical University,Urumqi 830000,China;Department of Nephrology,First Affiliated Hos-pital of Nephrology,First Affiliated Hospital of Xinjiang Medical University,Urumqi 830000,China)

机构地区：[1]新疆医科大学第一附属医院临床营养科,乌鲁木齐830000 [2]新疆医科大学附属中医医院内分泌科,乌鲁木齐830000 [3]新疆医科大学第一附属医院肾脏疾病中心肾病一科,乌鲁木齐830000

出　　处：《临床肾脏病杂志》2022年第10期840-846,共7页Journal Of Clinical Nephrology

基　　金：新疆维吾尔自治区自然科学基金(2018D01C206)。

摘　　要：目的探究硫酸镁通过Toll样受体4(toll-like receptor 4,TLR4)/核转录因子-κB(nuclear transcription factor-κB,NF-κB)通路对慢性肾衰竭(chronic renal failure,CRF)大鼠血管钙化(vascular calcification,VC)的影响。方法将SD大鼠按照随机数字法随机分为对照组、模型组、硫酸镁-L组(25%硫酸镁2 mL)、硫酸镁-H组(25%硫酸镁4 mL)、硫酸镁-H+吡咯烷二硫代氨基甲酸酯(pyrrolidine dithiocarbamate,PDTC)组(25%硫酸镁4 mL+100 mg/kg NF-κB抑制剂PDTC),10只/组;除对照组外,造模大鼠使用硫酸腺嘌呤混悬液灌胃3周,于4~12周,硫酸镁-L组、硫酸镁-H组、硫酸镁H+PDTC组灌胃相应剂量药物,模型组使用等体积生理盐水灌胃(1次/d),全程用高磷饲料饲喂;对照组于1~3周进行1.5%甲基纤维素灌胃,4~12周使用等量生理盐水灌胃,整个试用期均使用基础饲料喂养;全自动生化分析仪检测大鼠血清生化指标;HE染色观察大鼠肾组织病理学情况;钙盐染色液染色观察腹主动脉钙化情况;邻甲酚酞络合酮比色法检测大鼠腹主动脉血管壁钙含量;蛋白质印迹法检测大鼠腹主动脉核心结合因子α1(core binding factorα1,Cbfα1)、骨形态发生蛋白2(bone morpho⁃genic protein2,BMP2)及TLR4/NF-κB通路蛋白表达情况。结果与对照组相比,模型组大鼠血清中血尿素氮(blood urea nitrogen,BUN)、血肌酐(serum creatinine,Scr)、血磷、钙水平、肾组织病理损伤程度、腹主动脉钙化程度、Cbfα1、BMP2、TLR4、p-NF-κB p56/NF-κB p56表达显著增加,血清中镁水平显著降低(P<0.05);与模型组相比,硫酸镁-L组、硫酸镁-H组、硫酸镁-H+PDTC组BUN、Scr、血磷、钙水平、肾组织病理学程度、腹主动脉钙化程度、Cbfα1、BMP2、TLR4、p-NF-κB p56/NF-κB p56表达显著降低,镁水平显著增加(P<0.05);与硫酸镁-L组相比,硫酸镁-H组、硫酸镁-H+PDTC组BUN、Scr、血磷、钙水平、肾组织病理损伤程度、腹主动脉钙化程度、Cbfα1、BMP2、TLR4、p-NF-κObjective To explore the effect of magnesium sulfate on vascular calcification(VC)in rats with chronic renal failure(CRF)through the pathway of Toll-like receptor 4(TLR4)/nuclear transcription factor-κB(NF-κB).Methods A total of 50 Sprague-Dawley(SD)rats were randomized into five groups of control,model,magnesium sulfate-L(25%magnesium sulfate,2 mL),magnesium sulfate-H(25%magnesium sulfate,4 mL)and magnesium sulfate-H+PDTC(25%magnesium sul⁃fate,4 mL+NF-κB inhibitor PDTC,100 mg/kg)(n=10 each).Except for control group,model rats re⁃ceived adenine sulfate suspension by gavage for 3 weeks.From 4 to 12 weeks,magnesium sulfate-L,magnesium sulfate-H and magnesium sulfate-H+PDTC(pyrrolidine dithiocarbamate)had a gavage of corresponding doses of drugs.Model group received an equal volume of normal saline by gavage(once daily)and a high-phosphorus feed throughout;control group received 1.5%methylcellulose by gavage for 1-3 weeks,the same amount of normal saline by gavage for 4-12 weeks and basal feed during trial pe⁃riod;serum biochemical parameters were detected by an automatic biochemical analyzer;the pathology of kidney tissue was observed with hematoxylin-eosin(HE)stain;calcification of abdominal aorta was observed with von Kossa stain;calcium content in abdominal aortic vessel wall was detected by ocresolphthalein complex ketone colorimetry;the expressions of core binding factorα1(Cbfα1),bone morphogenic protein 2(BMP2)and TLR4/NF-κB pathway proteins in abdominal aorta were assayed by Western blot.Results As compared with control group,the levels of blood urea nitrogen(BUN),se⁃rum creatinine(Scr),blood phosphorus,calcium,degree of renal tissue pathological injury,abdominal aortic calcification and the expressions of Cbfα1,BMP2,TLR4,p-NF-κB p56/NF-κB p56 spiked mark⁃edly in model group while serum level of magnesium declined sharply(P<0.05);compared with model group,the levels of BUN,Scr,blood phosphorus,calcium,renal histopathology,abdominal aortic calci⁃fication and expressions of Cbfα1,BMP2,TLR

关 键 词：硫酸镁 TOLL样受体4 核转录因子-ΚB 慢性肾衰竭 血管钙化 

分 类 号：R692.5[医药卫生—泌尿科学]