七氟醚对大鼠缺血再灌注损伤后肾脏BSC1及AQP2表达的影响及对肾缺血再灌注损伤的保护作用的探讨
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摘要
目的：探讨吸入麻醉剂七氟醚对大鼠肾缺血-再灌注损伤（ischemiareperfusion,IRI）后Na+-2Clˉ-K+协同转运蛋白-1（Na+-2Clˉ-K+co-transporter-1，BSC1）,水通道蛋白-2（aquaporins-2 water channel，AQP2）表达的影响和七氟醚缺血前、后处理对急性肾缺血再灌注损伤的保护作用及其机制。
方法：SD雄性大鼠,随机均分为伪手术组（C）、对照组( I/ R组)、七氟醚预处理组（Spre-C）和七氟醚后处理组( Spost-C组)。根据肾动脉夹闭时间每组再分30、45、60 min三个亚组。建立大鼠急性肾缺血再灌注损伤模型,缺血再灌注后24h分别检测血清中肌酐( Cr )和尿素氮(BUN)含量，血清和肾组织［皮质加外髓外带（OSOM+C）和外髓内带加内髓（ISOM+IM）］超氧化物歧化酶( SOD)、丙二醛( MDA) ,髓过氧化物酶（MPO）活性。采集尿样检测尿量，尿比重，尿肌酐及内生肌酐清除率（Ccr）。采用Real Time RT-PCR、Western blot及免疫组织化学法分别测定肾组织［（OSOM+C）和（ISOM+IM）］BSC1、AQP2mRNA及蛋白表达情况，观察肾组织的病理学变化。探讨七氟醚于缺血前、后处理肾脏损伤程度。
结果：与C组比较,（1）I/ R ,Spre-C和Spost-C组血清BUN、Cr水平均显著增加( P< 0.05) , Spre-C (30,45 min)组和Spost-C (30,45 min)组BUN、Cr低于I/ R (30,45 min)组( P < 0 .05)。I/ R，Spre-C和Spost-C 60min组间无明显差异（P>0.05）；（2）I/ R、Spre-C和Spost-C组MDA、MPO明显升高，SOD显著下降，Spre-C (30,45 min)和Spost-C (30,45 min)组MDA、MPO低于I/ R (30,45 min)组( P < 0.05)，SOD高于I/ R(30,45 min)组( P <0.05)。I/ R，Spre-C和Spost-C 60min组间无明显差异（P＞0.05）；（3）Spre-C、Spost-C组肾组织病理损伤分级明显低于I/R组(P<0.05)。Spre-C(30,45 min)和Spost-C (30,45 min)组肾组织病理损伤分级低于I/R(30,45 min)组( P < 0.05)。60min时三组间无明显差异（P＞0.05）。（4）其它三组尿量增加，尿比重、尿Cr、内生肌酐清除率（Ccr）降低，组间无明显差异（P＞0.05）。（5）Real Time RT-PCR、Western blot及免疫组织化学法分别测定肾组织BSC1、AQP2mRNA及蛋白表达情况，结果显示，I/ R，Spre-C和Spost-C组BSC1、AQP2mRNA及蛋白表达表达均下调（P < 0.05），Spre-C (30,45 min)和Spost-C (30,45 min)组BSC1、AQP2mRNA及AQP2，BSC1蛋白表达低于I/R (30,45 min)组(P<0.05)。60min时三组间无明显差异（P＞0.05）。
结论：（1）七氟醚于缺血前、后处理对大鼠急性肾缺血再灌注损伤都具有保护作用。（2）肾脏缺血-再灌注损伤后BSC1、AQP2的表达显著下降。（3）七氟醚上调肾脏缺血-再灌注损伤后BSC1、AQP2的表达。（4）七氟醚可能通过上调BSC1、AQP2的表达对肾脏缺血-再灌注损伤起保护作用。
Objective：To investigate the effect of Sevoflurane on Na~+-2Cl~--K~+co-transporter-1（BSC1）and aquaporins-2 water channel (AQP2)expressionduring renal ischemia-reperfusion injury(IRI) and the protection andmechanism of sevoflurane on renal ischemia reperfusion injury in rats.
Methods：SD rats were allocated randomly and equally to operating group(group C), false ischemia reperfusion group(group I/R) , sevofluranereconditioning group(group Spre-c)and sevoflurane postconditioning group(group Spost-c).Every grope were divide into 3 subsets with 5 animales(30min,45min, 60min) according to the time of renal ischemia. All animalswere killed 24 h after ischemia reperfusion injury for histologic examination,Serum urea nitrogen(BUN)and creatinine ( Cr)were detected, superoxidedismutase (SOD) activity , myeloperoxidase (MPO) activity andconcentration of malonaldehyde (MDA) in renal tissue（OSOM+C andISOM+IM）and serum were examined.Collect urine to observe the change ofthe urine volume , urine specific gravity , urine creatinine and creatinineclearance.The levels of BSC1 in renal cortex and AQP2 in renal inner medullawas detected by Real Time RT-PCR,Western blot and immuno- histochemistry.Renal histopathology lesions were examined.Approach the degree of renalinjury.
Results:
1.The renal function of rats 24h after IRI was significantly differentbetween groups.Rats subjected to showed significant increase in serum Cr andBUN Compared with C group(P<0.05).The renal function changes caused by IRI were significantly improved by Spre-C(30,45 min) and Spost-C(30,45 min)treatments(P<0.05).There were no Significant difference among I/R(60min),Spre-C (60min)and Spost-C(60min) (P>0.05). And there were no significantdifference between Spre-C and Spost-C (p>0.05).
in significant down-regulation of the activities of SOD (P<0.05);whilecompared with I/R group(30,45 min)，Spre-C (30,45 min)andSpost-C(30,45min) treatments resulted in significant up-regulation of theiractivities(P<0.05); Compared with C group，the IRI rats resulted in significantincreases of the levels of MDA and MPO，While compared with I/Rgroup,Spre-C (30,45 min)and Spost-C(30,45 min) treatments resulted insignificant decreases of the levels of MDA and MPO，There were noSignificant difference among I/R(60min), Spre-C (60min)and Spost-C(60min)(P>0.05). And there were no significant difference between Spre-C andSpost-C (p>0.05).
3.Renal lRI resulted in significant renal injury as evidenced by tubularnecrosis medullary hemorrhage，eongestion，and development ofproteinaceous casts.In contrast，treatments of Spre-C(30,45 min) and Spost-C(30,45 min) group ameliorated these severe renal damages.According toPaller’s scores，Quantitative analysis showed a dramatically decreased score inboth Spre-C(30,45 min) and Spost-C (30,45 min) group compared withIR(30,45 min) group(P<0.05). There were no Significant difference amongI/R(60min), Spre-C (60min)and Spost-C(60min) (P>0.05). And there were nosignificant difference between Spre-C and Spost-C (p>0.05).
4.Compared with C group, the IRI rats resulted in significant increases ofthe volume of urine and decreases of the urine specific gravity , urine creatinineand creatinine clearance.
There were no Significant difference among I/R, Spre-C and Spost-C(P>0.05).
5.The Mrna and Protein expression of BSC1 and AQP2 was evaluated byRealTime-PCR,Western blot and immunohistochemistry. Compared with Cgroup,the IRI rats resulted In significant down-regulation of BSC1 andAQP2mRNA and Protein expression in renal(P<0.05); While compared withI/Rgroup,Spre-C (30,45 min)and Spost-C(30,45 min) treatments resulted insignificant up-regulation of BSC1 and AQP2mRNA and protein expression(P<0.05). There were no Significant difference among I/R(60min), Spre-C(60min)and Spost-C(60min) (P>0.05). And there were no significant differencebetween Spre-C and Spost-C (p>0.05).
Conelusion
1.Sevoflurane preconditioning and postconditioning were effectivelyprotected renal against IRI.
2.The fuction and structure of renal tissue were damaged by renal IRI inrats with the decrease of BSC1 and AQP2 Mrna and protein expression.
3.Sevoflurane up- regulating the expression of BSC1 and AQP2 inischemia-reperfusion.
4.The mechanism of isehemic preconditioning and postconditioningagainst renal IRI maybe associated to up- regulating BSC1 and AQP2 Mrnaand protein expression.
方法：SD雄性大鼠,随机均分为伪手术组（C）、对照组( I/ R组)、七氟醚预处理组（Spre-C）和七氟醚后处理组( Spost-C组)。根据肾动脉夹闭时间每组再分30、45、60 min三个亚组。建立大鼠急性肾缺血再灌注损伤模型,缺血再灌注后24h分别检测血清中肌酐( Cr )和尿素氮(BUN)含量，血清和肾组织［皮质加外髓外带（OSOM+C）和外髓内带加内髓（ISOM+IM）］超氧化物歧化酶( SOD)、丙二醛( MDA) ,髓过氧化物酶（MPO）活性。采集尿样检测尿量，尿比重，尿肌酐及内生肌酐清除率（Ccr）。采用Real Time RT-PCR、Western blot及免疫组织化学法分别测定肾组织［（OSOM+C）和（ISOM+IM）］BSC1、AQP2mRNA及蛋白表达情况，观察肾组织的病理学变化。探讨七氟醚于缺血前、后处理肾脏损伤程度。
结果：与C组比较,（1）I/ R ,Spre-C和Spost-C组血清BUN、Cr水平均显著增加( P< 0.05) , Spre-C (30,45 min)组和Spost-C (30,45 min)组BUN、Cr低于I/ R (30,45 min)组( P < 0 .05)。I/ R，Spre-C和Spost-C 60min组间无明显差异（P>0.05）；（2）I/ R、Spre-C和Spost-C组MDA、MPO明显升高，SOD显著下降，Spre-C (30,45 min)和Spost-C (30,45 min)组MDA、MPO低于I/ R (30,45 min)组( P < 0.05)，SOD高于I/ R(30,45 min)组( P <0.05)。I/ R，Spre-C和Spost-C 60min组间无明显差异（P＞0.05）；（3）Spre-C、Spost-C组肾组织病理损伤分级明显低于I/R组(P<0.05)。Spre-C(30,45 min)和Spost-C (30,45 min)组肾组织病理损伤分级低于I/R(30,45 min)组( P < 0.05)。60min时三组间无明显差异（P＞0.05）。（4）其它三组尿量增加，尿比重、尿Cr、内生肌酐清除率（Ccr）降低，组间无明显差异（P＞0.05）。（5）Real Time RT-PCR、Western blot及免疫组织化学法分别测定肾组织BSC1、AQP2mRNA及蛋白表达情况，结果显示，I/ R，Spre-C和Spost-C组BSC1、AQP2mRNA及蛋白表达表达均下调（P < 0.05），Spre-C (30,45 min)和Spost-C (30,45 min)组BSC1、AQP2mRNA及AQP2，BSC1蛋白表达低于I/R (30,45 min)组(P<0.05)。60min时三组间无明显差异（P＞0.05）。
结论：（1）七氟醚于缺血前、后处理对大鼠急性肾缺血再灌注损伤都具有保护作用。（2）肾脏缺血-再灌注损伤后BSC1、AQP2的表达显著下降。（3）七氟醚上调肾脏缺血-再灌注损伤后BSC1、AQP2的表达。（4）七氟醚可能通过上调BSC1、AQP2的表达对肾脏缺血-再灌注损伤起保护作用。
Objective：To investigate the effect of Sevoflurane on Na~+-2Cl~--K~+co-transporter-1（BSC1）and aquaporins-2 water channel (AQP2)expressionduring renal ischemia-reperfusion injury(IRI) and the protection andmechanism of sevoflurane on renal ischemia reperfusion injury in rats.
Methods：SD rats were allocated randomly and equally to operating group(group C), false ischemia reperfusion group(group I/R) , sevofluranereconditioning group(group Spre-c)and sevoflurane postconditioning group(group Spost-c).Every grope were divide into 3 subsets with 5 animales(30min,45min, 60min) according to the time of renal ischemia. All animalswere killed 24 h after ischemia reperfusion injury for histologic examination,Serum urea nitrogen(BUN)and creatinine ( Cr)were detected, superoxidedismutase (SOD) activity , myeloperoxidase (MPO) activity andconcentration of malonaldehyde (MDA) in renal tissue（OSOM+C andISOM+IM）and serum were examined.Collect urine to observe the change ofthe urine volume , urine specific gravity , urine creatinine and creatinineclearance.The levels of BSC1 in renal cortex and AQP2 in renal inner medullawas detected by Real Time RT-PCR,Western blot and immuno- histochemistry.Renal histopathology lesions were examined.Approach the degree of renalinjury.
Results:
1.The renal function of rats 24h after IRI was significantly differentbetween groups.Rats subjected to showed significant increase in serum Cr andBUN Compared with C group(P<0.05).The renal function changes caused by IRI were significantly improved by Spre-C(30,45 min) and Spost-C(30,45 min)treatments(P<0.05).There were no Significant difference among I/R(60min),Spre-C (60min)and Spost-C(60min) (P>0.05). And there were no significantdifference between Spre-C and Spost-C (p>0.05).
in significant down-regulation of the activities of SOD (P<0.05);whilecompared with I/R group(30,45 min)，Spre-C (30,45 min)andSpost-C(30,45min) treatments resulted in significant up-regulation of theiractivities(P<0.05); Compared with C group，the IRI rats resulted in significantincreases of the levels of MDA and MPO，While compared with I/Rgroup,Spre-C (30,45 min)and Spost-C(30,45 min) treatments resulted insignificant decreases of the levels of MDA and MPO，There were noSignificant difference among I/R(60min), Spre-C (60min)and Spost-C(60min)(P>0.05). And there were no significant difference between Spre-C andSpost-C (p>0.05).
3.Renal lRI resulted in significant renal injury as evidenced by tubularnecrosis medullary hemorrhage，eongestion，and development ofproteinaceous casts.In contrast，treatments of Spre-C(30,45 min) and Spost-C(30,45 min) group ameliorated these severe renal damages.According toPaller’s scores，Quantitative analysis showed a dramatically decreased score inboth Spre-C(30,45 min) and Spost-C (30,45 min) group compared withIR(30,45 min) group(P<0.05). There were no Significant difference amongI/R(60min), Spre-C (60min)and Spost-C(60min) (P>0.05). And there were nosignificant difference between Spre-C and Spost-C (p>0.05).
4.Compared with C group, the IRI rats resulted in significant increases ofthe volume of urine and decreases of the urine specific gravity , urine creatinineand creatinine clearance.
There were no Significant difference among I/R, Spre-C and Spost-C(P>0.05).
5.The Mrna and Protein expression of BSC1 and AQP2 was evaluated byRealTime-PCR,Western blot and immunohistochemistry. Compared with Cgroup,the IRI rats resulted In significant down-regulation of BSC1 andAQP2mRNA and Protein expression in renal(P<0.05); While compared withI/Rgroup,Spre-C (30,45 min)and Spost-C(30,45 min) treatments resulted insignificant up-regulation of BSC1 and AQP2mRNA and protein expression(P<0.05). There were no Significant difference among I/R(60min), Spre-C(60min)and Spost-C(60min) (P>0.05). And there were no significant differencebetween Spre-C and Spost-C (p>0.05).
Conelusion
1.Sevoflurane preconditioning and postconditioning were effectivelyprotected renal against IRI.
2.The fuction and structure of renal tissue were damaged by renal IRI inrats with the decrease of BSC1 and AQP2 Mrna and protein expression.
3.Sevoflurane up- regulating the expression of BSC1 and AQP2 inischemia-reperfusion.
4.The mechanism of isehemic preconditioning and postconditioningagainst renal IRI maybe associated to up- regulating BSC1 and AQP2 Mrnaand protein expression.
引文
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