丙泊酚对叶间动脉缺血再灌注损伤的保护作用：机制可能为降低Cx43的异常表达
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The Protective Effect of Propofol Against Ischemia-Reperfusion Injury in the Interlobar Arteries: Reduction of Abnormal Cx43 Expression as a Possible Mechanism
背景与目的
本研究的目的是观察丙泊酚是否通过影响缝隙连接蛋白43（Cx43）的表达发挥对大鼠肾脏叶间动脉缺血再灌注损伤（IRI）的保护作用。
方 法
本研究将雄性SD大鼠随机分为对照组、假手术组（假手术组）、缺血再灌注组（IR组）、丙泊酚组（丙泊酚+ IR组）和脂肪乳剂组（Intralipid组）。通过切除右肾并对左肾行非侵入性动脉闭塞来制备缺血/再灌注模型。 肾脏缺血再灌注45分钟后，采用自动生化分析仪测定血尿素氮（BUN）和血清肌酐（SCr）; 使用苏木精和伊红（HE）染色观察肾组织的病理学变化，并使用压力机械图技术检测叶间动脉的血管收缩活性。通过蛋白质印迹法测定肾动脉横截面中Cx43蛋白的表达。
结 果
本研究结果表明缺血再灌注损伤后大鼠的BUN和SCr明显增加;此外，我们也观察到一些细胞凝固性坏死和细胞脱落、核染色质凝固、细胞质液泡变性、肾间质血管高度充血和明显炎性细胞浸润，以局灶性出血为特征。此外，肾叶间动脉的收缩活性显著降低，肾叶间动脉的张力显著增加。在应用缝隙连接通道阻断剂2-APB和Gap27后，血管的收缩速度和血管收缩率均降低。此外，Cx43在肾脏组织中的表达显著增加。缺血再灌注后24小时的损伤比缺血再灌注后4小时的损伤更严重。然而，经丙泊酚预处理后，无论在缺血再灌注后的4小时或24小时，Cx43的表达明显减少，且所有类型的肾损伤均逆转。
结 论
本研究表明丙泊酚可通过减少缝隙连接蛋白Cx43的异常表达来减轻缺血再灌注损伤。并揭示了丙泊酚对IRI作用的新机制，我们希望该发现将为IRI的治疗带来新的方法。
原始文献摘要
Chang YC, Xue WJ, Ji W, Wang Y, WangYP, Shi WY, Shan LY, Zhang L, Tan CY, MaKT, Li L, Si JQ. The Protective Effect of Propofol Against Ischemia-Reperfusion Injury in the
Interlobar Arteries: Reduction of Abnormal Cx43 Expression as a Possible Mechanism. Kidney Blood Press Res. 2018 Oct 22;43(5):1607-1622. doi: 10.1159/000494450.
BACKGROUND/AIMS:
This experimental study aims to observe whether the protective effect of propofol against renal ischemia-reperf usion injury (IRI) in the rat
interlobar artery occurs through altered expression of the gap junction protein connexin 43 (Cx43).
METHODS:
This study randomly divided male Sprague Dawley (SD) rats into an
untreated control group, a sham-operated control group (sham group), an ischemia reperfusion group (IR group), a propofol group (propof ol+IR group) and a fat emulsion group (Intralipid group). The ischemia/reperf usion model was prepared through resection of the right kidney and noninvasive arterial occlusion of the lef t kidney. Forty-five minutes af ter renal ischemia-reperf usion, an automatic biochemical analyzer was employed to measure blood urea nitrogen (BUN) and serum creatinine (SCr); changes in renal tissue pathology were observed using hematoxylin and eosin (HE) staining, and the vasomotor activity of the interlobar artery was detected using a pressure mechanogram technique. The protein expression of Cx43 in renal artery cross-sections was determined through western blotting.
RESULTS:
The experimental study confirmed that the BUN and SCr of rats
markedly increased af ter ischemia-reperf usion injury; additionally, we observed some coagulation necrosis and shedding of cells, some solidification of nuclear chromatin, degeneration of cytoplasmic vacuoles, high renal interstitial vascular congestion and obvious inflammatory cell infiltration, characterized by f ocal hemorrhages. Furthermore, the contraction activity of the renal interlobar artery greatly decreased, and the tension of the arteries in the renal lobe increased remarkably. Af ter the gap junction blocking agents 2-APB and Gap27 were applied, the systolic velocity of blood vessels and the vascular contraction rate both decreased. In addition, the expression of Cx43 in kidney tissues increased markedly. The damage was more severe af ter 24 h of ischemic reperf usion than after only 4 h. However, af ter pretreatment withpropof ol, regardless of whether ischemia-reperf usion was applied f or 4 h or 24 h, the previously increased expression of Cx43 decreased obviously, and all f orms of renal damage were reversed.
CONCLUSION:
Our research suggests new ways for propofol to relieve ischemia-reperf usion injury by decreasing the abnormal expression of the gap junction protein Cx43.This study reveals a novel mechanism f or the action of propofol against IRI, and we hope this finding will lead to new treatments for IRI.
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