中国药理学与毒理学杂志
中國藥理學與毒理學雜誌
중국약이학여독이학잡지
CHINESE JOURNAL OF PHARMACOLOGY AND TOXICOLOGY
2014年
3期
358-361
,共4页
张玉霞%刘国玲%王家勤%李宜川%胡灵卫%芦琨
張玉霞%劉國玲%王傢勤%李宜川%鬍靈衛%蘆琨
장옥하%류국령%왕가근%리의천%호령위%호곤
雷公藤多苷%糖尿病肾病%过氧化氢酶%谷胱甘肽过氧化物酶%丙二醛
雷公籐多苷%糖尿病腎病%過氧化氫酶%穀胱甘肽過氧化物酶%丙二醛
뢰공등다감%당뇨병신병%과양화경매%곡광감태과양화물매%병이철
Tripterygium wilfordii polyglycoside%diabetic nephropathy%catalase%glutathione peroxi-dase%malondialdehyde
目的:观察雷公藤多苷(TWP)对糖尿病性肾病大鼠的抗氧化应激作用。方法大鼠ip给予链脲佐菌素(STZ)制备DN模型。3周后造模成功,ig给予TWP 4.5,9.0和18.0 mg·kg -1,每天1次,连续8周。实验过程中观察大鼠的体质量、毛发和精神状况等。实验结束前2 d 将大鼠置代谢笼,收集24 h尿液,用于检测24 h尿白蛋白排泄率(24 h UAER)。用药8周末,自动生化分析仪检测血肌酐(Scr)、尿素氮(BUN)和尿肌酐(Ucr)水平,并计算肌酐清除率(Clcr);可见光方法检测血清过氧化氢酶(CAT)活性,比色法测定血清超氧阴离子(O2÷)水平。比色法测定肾组织谷胱甘肽过氧化物酶(GSH-Px)活性,硫代巴比妥酸缩合法检测丙二醛(MD A)含量;H E染色观察肾组织病理改变。结果与正常对照组相比,模型对照组大鼠逐渐出现多饮、多尿、多食、消瘦以及反应迟钝、毛发枯黄、尾巴苍白湿冷、精神萎靡等现象;空腹血糖、BUN和24 h UAER均显著增高(P<0.01),Clcr明显降低(P<0.01);血清CAT活性和肾组织中GSH-Px活性明显降低(P<0.01),血清O2÷水平和肾组织MDA含量明显升高(P<0.01);肾小球肥大,系膜细胞增生,肾小球变形。与模型对照组比较,ig给予TWP 9和18 mg·kg -1可改善大鼠一般状况,BUN和24 h UAER明显降低(P<0.01),Clcr和血清 CAT 显著升高(P<0.01),O2÷和MDA含量降低(P<0.01), GSH-Px明显升高(P<0.01),肾组织病理变化明显减轻。TWP 4.5 mg·kg -1对上述指标均无明显影响。结论TWP能明显改善糖尿病性肾病大鼠的肾功能,其机制可能与抑制氧化应激和增强机体抗氧化能力相关。
目的:觀察雷公籐多苷(TWP)對糖尿病性腎病大鼠的抗氧化應激作用。方法大鼠ip給予鏈脲佐菌素(STZ)製備DN模型。3週後造模成功,ig給予TWP 4.5,9.0和18.0 mg·kg -1,每天1次,連續8週。實驗過程中觀察大鼠的體質量、毛髮和精神狀況等。實驗結束前2 d 將大鼠置代謝籠,收集24 h尿液,用于檢測24 h尿白蛋白排洩率(24 h UAER)。用藥8週末,自動生化分析儀檢測血肌酐(Scr)、尿素氮(BUN)和尿肌酐(Ucr)水平,併計算肌酐清除率(Clcr);可見光方法檢測血清過氧化氫酶(CAT)活性,比色法測定血清超氧陰離子(O2÷)水平。比色法測定腎組織穀胱甘肽過氧化物酶(GSH-Px)活性,硫代巴比妥痠縮閤法檢測丙二醛(MD A)含量;H E染色觀察腎組織病理改變。結果與正常對照組相比,模型對照組大鼠逐漸齣現多飲、多尿、多食、消瘦以及反應遲鈍、毛髮枯黃、尾巴蒼白濕冷、精神萎靡等現象;空腹血糖、BUN和24 h UAER均顯著增高(P<0.01),Clcr明顯降低(P<0.01);血清CAT活性和腎組織中GSH-Px活性明顯降低(P<0.01),血清O2÷水平和腎組織MDA含量明顯升高(P<0.01);腎小毬肥大,繫膜細胞增生,腎小毬變形。與模型對照組比較,ig給予TWP 9和18 mg·kg -1可改善大鼠一般狀況,BUN和24 h UAER明顯降低(P<0.01),Clcr和血清 CAT 顯著升高(P<0.01),O2÷和MDA含量降低(P<0.01), GSH-Px明顯升高(P<0.01),腎組織病理變化明顯減輕。TWP 4.5 mg·kg -1對上述指標均無明顯影響。結論TWP能明顯改善糖尿病性腎病大鼠的腎功能,其機製可能與抑製氧化應激和增彊機體抗氧化能力相關。
목적:관찰뢰공등다감(TWP)대당뇨병성신병대서적항양화응격작용。방법대서ip급여련뇨좌균소(STZ)제비DN모형。3주후조모성공,ig급여TWP 4.5,9.0화18.0 mg·kg -1,매천1차,련속8주。실험과정중관찰대서적체질량、모발화정신상황등。실험결속전2 d 장대서치대사롱,수집24 h뇨액,용우검측24 h뇨백단백배설솔(24 h UAER)。용약8주말,자동생화분석의검측혈기항(Scr)、뇨소담(BUN)화뇨기항(Ucr)수평,병계산기항청제솔(Clcr);가견광방법검측혈청과양화경매(CAT)활성,비색법측정혈청초양음리자(O2÷)수평。비색법측정신조직곡광감태과양화물매(GSH-Px)활성,류대파비타산축합법검측병이철(MD A)함량;H E염색관찰신조직병리개변。결과여정상대조조상비,모형대조조대서축점출현다음、다뇨、다식、소수이급반응지둔、모발고황、미파창백습랭、정신위미등현상;공복혈당、BUN화24 h UAER균현저증고(P<0.01),Clcr명현강저(P<0.01);혈청CAT활성화신조직중GSH-Px활성명현강저(P<0.01),혈청O2÷수평화신조직MDA함량명현승고(P<0.01);신소구비대,계막세포증생,신소구변형。여모형대조조비교,ig급여TWP 9화18 mg·kg -1가개선대서일반상황,BUN화24 h UAER명현강저(P<0.01),Clcr화혈청 CAT 현저승고(P<0.01),O2÷화MDA함량강저(P<0.01), GSH-Px명현승고(P<0.01),신조직병리변화명현감경。TWP 4.5 mg·kg -1대상술지표균무명현영향。결론TWP능명현개선당뇨병성신병대서적신공능,기궤제가능여억제양화응격화증강궤체항양화능력상관。
OBJECTIVE ToinvestigatethepossibleprotectiveeffectofTripterygiumwilfordiipolyg-lycoside (TWP ) on experi mental diabetic nephropathy (D N ) rats and its possible mechanis m. METHODS Thediabeticmodelwasinducedbyasingleintraperitonealinjectionofstreptozotocin (STZ)65 mg·kg -1 .Three weeks after modeling,TWP 4.5,9.0 and 1 8.0 mg·kg -1 was ig given to rats,once daily,for 8 consecutive weeks.During the experiment,the changes of body mass,hair, mental health of rats were observed.Two days before the end of the experi ment,the rats were placed into metabolic cages to collect 24 h urine in order to detect 24 h urinary albu min excretion rate (UAER). The rats were given TWP for 8 weeks and anesthetized with 1 0%chloral hydrate.The blood was collect-ed fro m the heart and centrifuged,seru m creatinine and urine creatinine were measured,and creatinine clearance (Clcr)was calculated.Blood urea nitrogen (BUN)and the serum catalase (CAT)activity were tested by optical method while the level of seru m superoxide oxygen anion(O2÷)was tested by col-orimetry.The level of malondialdehyde(MDA)was determined by thiobarbituric acid condensation,and glutathione peroxidase (GSH-Px)activity was tested by colorimetry.The right kidney was HE stained to observepathologicalchanges.RESULTS Comparedwithnormalcontrolgroup,theratsinmodel control group developed polydipsia,polyuria,polyphagia,body mass loss,unresponsiveness,brown hair,pale tail and apathy clammy.Besides,blood glucose,BUN and 24 h UAER were significantly higher (P<0.01 ),but Clcr was lower (P<0.01 ).The activity of serum CAT and GSH-Px in renal tissue was significantly lower(P<0.01 ),while the level of serum O2÷ and MDA in the renal tissue was significantly higher(P<0.01 ).Compared with model control group,TWP 9.0 and 18.0 mg·kg -1 could improve the general condition of rats.BUN and 24 h UAER were obviously reduced(P<0.01 ),Clcr and serum CAT were increased obviously(P<0.01 ),the level of MDA and O2÷ were reduced obviously(P<0.01 ),and GSH-Px level was increased(P<0.01 ).TWP 9.0 and 18.0 mg·kg -1 could significantly im-prove the renal histopathological changes of rats.TWP 4.5 mg·kg -1 had no significant effect on the aboveindicators.CONCLUSION TWPhasprotectiveeffectontherenalfunctionofexperimentalDN rats.The mechanis m may be related to inhibition of the oxidative stress and enhance ment of the body antioxidant capacity.