中国药理学通报
中國藥理學通報
중국약이학통보
CHINESE PHARMACOLOGICAL BULLETIN
2015年
2期
216-220,221
,共6页
刘新文%黄振光%杨玉芳%丘岳%温燕
劉新文%黃振光%楊玉芳%丘嶽%溫燕
류신문%황진광%양옥방%구악%온연
三七总皂苷%顺铂肾损害%线粒体途径%凋亡%caspase-9%Bax%Bcl-2
三七總皂苷%順鉑腎損害%線粒體途徑%凋亡%caspase-9%Bax%Bcl-2
삼칠총조감%순박신손해%선립체도경%조망%caspase-9%Bax%Bcl-2
panax notoginseng saponins( PNS)%cispla-tin-induced renal damage%mitochondria pathway%apop-tosis%caspase-9%Bax%Bcl-2
目的:探讨三七总皂苷( PNS)通过线粒体途径对顺铂肾损伤大鼠肾组织细胞凋亡的影响。方法将36只♂ SD大鼠随机分为空白对照组、顺铂模型组、顺铂+PNS组;在给药8 d后,检测大鼠血清肌酐( Cr)、尿素氮( BUN)和尿β-N-乙酰胺基葡萄糖苷酶( NAG)水平。采用HE染色观察病理变化,利用透射电子显微镜观察大鼠肾脏线粒体形态,采用原位末端缺口标记法( TUNEL染色)检测肾细胞凋亡情况,通过免疫组化SP法检测凋亡相关蛋白Bax、caspase-9的表达,并采用Western blot检测Bcl-2蛋白的表达情况。结果与空白对照组比较,顺铂模型组大鼠血清Cr、BUN和尿NAG水平明显升高(P<0.01),肾小管上皮细胞线粒体损伤严重,肾组织的细胞凋亡率明显增加( P<0.01),肾组织Bax、caspase-9及Bcl-2表达均明显增强( P<0.01);与顺铂模型组比较,顺铂+PNS组血清Cr、BUN和尿NAG水平明显降低(P<0.01),肾小管上皮细胞线粒体损害明显改善,肾组织细胞凋亡率和Bax、caspase-9表达水平均明显降低( P<0.01),Bcl-2的表达则明显增强(P<0.01)。结论 PNS可能通过增加抑凋亡蛋白Bcl-2表达,减少促凋亡蛋白Bax和凋亡相关蛋白caspase-9的表达来调节细胞凋亡,从而发挥保护顺铂肾损害的作用。
目的:探討三七總皂苷( PNS)通過線粒體途徑對順鉑腎損傷大鼠腎組織細胞凋亡的影響。方法將36隻♂ SD大鼠隨機分為空白對照組、順鉑模型組、順鉑+PNS組;在給藥8 d後,檢測大鼠血清肌酐( Cr)、尿素氮( BUN)和尿β-N-乙酰胺基葡萄糖苷酶( NAG)水平。採用HE染色觀察病理變化,利用透射電子顯微鏡觀察大鼠腎髒線粒體形態,採用原位末耑缺口標記法( TUNEL染色)檢測腎細胞凋亡情況,通過免疫組化SP法檢測凋亡相關蛋白Bax、caspase-9的錶達,併採用Western blot檢測Bcl-2蛋白的錶達情況。結果與空白對照組比較,順鉑模型組大鼠血清Cr、BUN和尿NAG水平明顯升高(P<0.01),腎小管上皮細胞線粒體損傷嚴重,腎組織的細胞凋亡率明顯增加( P<0.01),腎組織Bax、caspase-9及Bcl-2錶達均明顯增彊( P<0.01);與順鉑模型組比較,順鉑+PNS組血清Cr、BUN和尿NAG水平明顯降低(P<0.01),腎小管上皮細胞線粒體損害明顯改善,腎組織細胞凋亡率和Bax、caspase-9錶達水平均明顯降低( P<0.01),Bcl-2的錶達則明顯增彊(P<0.01)。結論 PNS可能通過增加抑凋亡蛋白Bcl-2錶達,減少促凋亡蛋白Bax和凋亡相關蛋白caspase-9的錶達來調節細胞凋亡,從而髮揮保護順鉑腎損害的作用。
목적:탐토삼칠총조감( PNS)통과선립체도경대순박신손상대서신조직세포조망적영향。방법장36지♂ SD대서수궤분위공백대조조、순박모형조、순박+PNS조;재급약8 d후,검측대서혈청기항( Cr)、뇨소담( BUN)화뇨β-N-을선알기포도당감매( NAG)수평。채용HE염색관찰병리변화,이용투사전자현미경관찰대서신장선립체형태,채용원위말단결구표기법( TUNEL염색)검측신세포조망정황,통과면역조화SP법검측조망상관단백Bax、caspase-9적표체,병채용Western blot검측Bcl-2단백적표체정황。결과여공백대조조비교,순박모형조대서혈청Cr、BUN화뇨NAG수평명현승고(P<0.01),신소관상피세포선립체손상엄중,신조직적세포조망솔명현증가( P<0.01),신조직Bax、caspase-9급Bcl-2표체균명현증강( P<0.01);여순박모형조비교,순박+PNS조혈청Cr、BUN화뇨NAG수평명현강저(P<0.01),신소관상피세포선립체손해명현개선,신조직세포조망솔화Bax、caspase-9표체수평균명현강저( P<0.01),Bcl-2적표체칙명현증강(P<0.01)。결론 PNS가능통과증가억조망단백Bcl-2표체,감소촉조망단백Bax화조망상관단백caspase-9적표체래조절세포조망,종이발휘보호순박신손해적작용。
Aim To investigate the effects of panax nonstaining saponins ( PNS ) on the apoptosis of renal cells induced by cisplatin through the path of mitochon-drion . Methods Male Sprague-Dawley( SD) rats were randomized divided into normal control group, cisplatin model group and the cisplatin+PNS group,with 12 rats of each group. Animals were sacrificed to determine the N-acetyl-β-D-Glucosaminidase ( NAG ) in urine, blood urea nitrogen ( BUN) and serum creatinine ( Cr) concentrations after 8d of intraperitoneal injection. HE-staining was employed to observe renal pathologies. Transmission electron microscopy ( TEM ) was em-ployed to observe the mitochondria of the rats′ injured kidney region. TUNEL staining was employed to detect the distribution of apoptotic cells. Immunnohistochem-istry was used to detect Bax and caspase-9 expression, and expression of Bcl-2 protein was detected by West-ern blot. Results Compared with the normal control group, contents of BUN, serum Cr and urinary NAG levels of rat in the cisplatin model group were increased ( P <0. 01 ) , and some mitochondria of the epithelial cells of renal tubules got injured seriously. The apopto-sis rate of kidney cell was increased ( P<0. 01 ) . The expression of Bax,caspase-9 and Bcl-2 proteins was in-creased ( P < 0. 01 ) . Compared with the cisplatin model group, contents of BUN, serum Cr and urinary NAG levels of rats in the cisplatin model group were decreased ( P <0. 01 ) , and some mitochondria of the epithelial cells of renal tubules were significantly im-proved. The apoptosis rate of kidney cell was decreased ( P<0. 01 ) . The expression of Bax and caspase-9 pro-tein was decreased (P<0. 01),but Bcl-2 protein was increased ( P < 0. 01 ) . Conclusion PNS may in-crease the expression of Bcl-2 protein and decrease the expression of Bax and caspase-9 proteins, which may play a protective role in cisplatin nephritic damage.