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
4期
510-514
,共5页
郭芳%孙应彪%李盛%苏莉%刘志飞%赵迟
郭芳%孫應彪%李盛%囌莉%劉誌飛%趙遲
곽방%손응표%리성%소리%류지비%조지
百草枯%氯沙坦%肺损伤%氧化应激%NF-κB
百草枯%氯沙坦%肺損傷%氧化應激%NF-κB
백초고%록사탄%폐손상%양화응격%NF-κB
paraquat%Iosartan%Iung injury%oxidative stress%NF-κB
目的:探讨氯沙坦对百草枯(PQ)急性染毒大鼠肺组织氧化损伤的影响。方法选择成年雄性SD 大鼠随机分为正常对照组、PQ 染毒组(一次性 ig 给予 PQ 40 mg·kg-1)及染毒后氯沙坦干预7和14 d组(一次性 ig 给予 PQ 后,每天 ig 给予氯沙坦10 mg·kg-1连续7和14 d)。第16天处死大鼠取肺组织,常规制备肺组织病理切片,HE 染色观察肺组织病理改变。用分光光度法测定肺组织匀浆中超氧化物歧化酶(SOD)、过氧化氢酶(CAT)活性及总抗氧化能力(T-AOC)和脂质过氧化物(LPO)含量。采用实时荧光定量 PCR 检测肺组织 NF-κB mRNA 表达水平。结果病理观察结果显示,PQ 急性染毒后大鼠出现明显的肺损伤和肺组织纤维化,经氯沙坦干预后病理改变均有一定程度的逆转。与正常对照组比较,PQ 染毒组大鼠肺组织匀浆中 SOD 和 CAT 活性明显降低( P ﹤0.05),T-AOC 下降( P ﹤0.05),LPO 含量明显升高(P﹤0.05)。与 PQ 染毒组比较,氯沙坦干预7和14 d 组 SOD 和 CAT 活性及 T-AOC 升高(P﹤0.05),LPO含量明显降低(P﹤0.05),其中氯沙坦干预7和14 d 组 T-AOC 和 LPO 含量以及氯沙坦干预14 d 组 SOD和 CAT 活性基本恢复接近至正常水平。实时荧光定量 PCR 结果表明,PQ 染毒后肺组织 NF-κB mRNA 表达水平明显升高(P﹤0.05)。与 PQ 染毒组比较,氯沙坦干预7和14 d 组 NF-κB mRNA 表达降低( P﹤0.05),恢复接近正常水平。结论氧化应激参与 PQ 急性肺损伤过程,氯沙坦通过提高肺组织的抗氧化能力和降低 NF-κB mRNA 表达而发挥对肺组织的保护作用。
目的:探討氯沙坦對百草枯(PQ)急性染毒大鼠肺組織氧化損傷的影響。方法選擇成年雄性SD 大鼠隨機分為正常對照組、PQ 染毒組(一次性 ig 給予 PQ 40 mg·kg-1)及染毒後氯沙坦榦預7和14 d組(一次性 ig 給予 PQ 後,每天 ig 給予氯沙坦10 mg·kg-1連續7和14 d)。第16天處死大鼠取肺組織,常規製備肺組織病理切片,HE 染色觀察肺組織病理改變。用分光光度法測定肺組織勻漿中超氧化物歧化酶(SOD)、過氧化氫酶(CAT)活性及總抗氧化能力(T-AOC)和脂質過氧化物(LPO)含量。採用實時熒光定量 PCR 檢測肺組織 NF-κB mRNA 錶達水平。結果病理觀察結果顯示,PQ 急性染毒後大鼠齣現明顯的肺損傷和肺組織纖維化,經氯沙坦榦預後病理改變均有一定程度的逆轉。與正常對照組比較,PQ 染毒組大鼠肺組織勻漿中 SOD 和 CAT 活性明顯降低( P ﹤0.05),T-AOC 下降( P ﹤0.05),LPO 含量明顯升高(P﹤0.05)。與 PQ 染毒組比較,氯沙坦榦預7和14 d 組 SOD 和 CAT 活性及 T-AOC 升高(P﹤0.05),LPO含量明顯降低(P﹤0.05),其中氯沙坦榦預7和14 d 組 T-AOC 和 LPO 含量以及氯沙坦榦預14 d 組 SOD和 CAT 活性基本恢複接近至正常水平。實時熒光定量 PCR 結果錶明,PQ 染毒後肺組織 NF-κB mRNA 錶達水平明顯升高(P﹤0.05)。與 PQ 染毒組比較,氯沙坦榦預7和14 d 組 NF-κB mRNA 錶達降低( P﹤0.05),恢複接近正常水平。結論氧化應激參與 PQ 急性肺損傷過程,氯沙坦通過提高肺組織的抗氧化能力和降低 NF-κB mRNA 錶達而髮揮對肺組織的保護作用。
목적:탐토록사탄대백초고(PQ)급성염독대서폐조직양화손상적영향。방법선택성년웅성SD 대서수궤분위정상대조조、PQ 염독조(일차성 ig 급여 PQ 40 mg·kg-1)급염독후록사탄간예7화14 d조(일차성 ig 급여 PQ 후,매천 ig 급여록사탄10 mg·kg-1련속7화14 d)。제16천처사대서취폐조직,상규제비폐조직병리절편,HE 염색관찰폐조직병리개변。용분광광도법측정폐조직균장중초양화물기화매(SOD)、과양화경매(CAT)활성급총항양화능력(T-AOC)화지질과양화물(LPO)함량。채용실시형광정량 PCR 검측폐조직 NF-κB mRNA 표체수평。결과병리관찰결과현시,PQ 급성염독후대서출현명현적폐손상화폐조직섬유화,경록사탄간예후병리개변균유일정정도적역전。여정상대조조비교,PQ 염독조대서폐조직균장중 SOD 화 CAT 활성명현강저( P ﹤0.05),T-AOC 하강( P ﹤0.05),LPO 함량명현승고(P﹤0.05)。여 PQ 염독조비교,록사탄간예7화14 d 조 SOD 화 CAT 활성급 T-AOC 승고(P﹤0.05),LPO함량명현강저(P﹤0.05),기중록사탄간예7화14 d 조 T-AOC 화 LPO 함량이급록사탄간예14 d 조 SOD화 CAT 활성기본회복접근지정상수평。실시형광정량 PCR 결과표명,PQ 염독후폐조직 NF-κB mRNA 표체수평명현승고(P﹤0.05)。여 PQ 염독조비교,록사탄간예7화14 d 조 NF-κB mRNA 표체강저( P﹤0.05),회복접근정상수평。결론양화응격삼여 PQ 급성폐손상과정,록사탄통과제고폐조직적항양화능력화강저 NF-κB mRNA 표체이발휘대폐조직적보호작용。
OBJECTlVE To expIore the intervention effect of Iosartan on the Iung oxidative injury in-duced by paraquat(PQ). METHODS AduIt maIe SD rats were randomIy divided into 4 groups:normaI controI group,PQ intoxication group(rats were treated with singIe ig PQ 40 mg·kg-1 ),Iosartan inter-vention for 7 and 14 d groups(rats were ig given Iosartan 10 mg·kg-1 daiIy for 7 and 14 consecutive days after PQ was given). AII rats were sacrificed on the 16th day to obtain Iung tissues. HE staining was used to observe the Iung pathoIogicaI changes. The activities of superoxide dismutase(SOD),cataIase (CAT)and totaI antioxidant capacity(T-AOC)and content of Iipid peroxide(LPO)were detected by spectrophotometry. ReaI-time quantitative PCR was used to investigate the NF-κB mRNA expression in Iung tissue. RESULTS PathoIogicaI examination showed that acute Iung injury and significant Iung fibro-sis appeared in PQ intoxication group but were reversed by Iosartan. The IeveIs of SOD,CAT and T-AOC decreased whiIe the content of LPO in PQ intoxication group increased significantIy compared with controI group(P﹤0.05). Compared with PQ intoxication group,the IeveIs of SOD,CAT and T-AOC in-creased and the content of LPO decreased in Iosartan intervention for 7 and 14 d groups(P﹤0.05),and the IeveIs of T-AOC and LPO in Iosartan intervention for 7 and 14 d groups and the activities of SOD and CAT in Iosartan intervention for 14 d group nearIy returned to normaI. The mRNA expression of NF-κB was upreguIated after rats were exposed to PQ,downreguIated in Iosartan intervention for 7 and 14 d groups in rat Iung tissues( P﹤0.05),but nearIy returned to normaI. CONCLUSlON Oxidative stress may be invoIved in the acute PQ poisoning process and Iosartan might have intervention effect on acute PQ Iung damage by improving the antioxidant capacity and downreguIating the mRNA expression of NF-κB.