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| 辣椒素减轻大鼠肾缺血-再灌注损伤的作用 |
| Effect of capsaicin on renal ischemia-reperfusion injury in rats |
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| DOI：10.12089/jca.2019.04.018 |
| 中文关键词: 辣椒素 缺血-再灌注损伤 细胞凋亡 炎性因子 IL-6/JAK2/STAT3通路 |
| 英文关键词: Capsaicin Ischemia-reperfusion injury Apoptosis Inflammatory factors IL-6/JAK2/STAT3 pathway |
| 基金项目:国家自然科学基金（81400260） |
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| 中文摘要: |
目的 探讨辣椒素减轻大鼠肾缺血-再灌注损伤（ischemia-reperfusion injury,IRI）的作用及其机制。
方法 成年健康清洁雄性SD大鼠40只，体重200～250 g，随机分为四组：假手术组（S组）、缺血-再灌注组（IR组）、辣椒素组（CAP组）和辣椒素+辣椒平组（CPZ组），每组10只。S组仅分离双侧肾蒂不结扎，IR组、CAP组和CPZ组通过动脉夹夹闭双侧肾蒂45 min，再灌注24 h的方法建立肾缺血-再灌注模型。S组与IR组在同时点注射等容量生理盐水，CAP组和CPZ组大鼠于缺血前30 min经腹腔注射辣椒素30 mg/kg。CPZ组大鼠于缺血前45 min经腹腔注射辣椒平20 mg/kg。于再灌注24 h后取血标本检测大鼠血清肌酐（Cr）、尿素氮（BUN）、白细胞介素-6（IL-6），肿瘤坏死因子-α（TNF-α）和白细胞介素-10（IL-10）浓度。采用Western blot法检测Janus蛋白酪氨酸激酶2（JAK2）、信号转导子及转录激活子3（STAT3）、磷酸化Janus蛋白酪氨酸激酶2（P-JAK2）、磷酸化信号转导子及转录激活子3（P-STAT3）和caspase-3的蛋白含量。取肾组织观察组织病理学改变，检测凋亡率（AI）。
结果 与S组比较，IR组、CAP组和CPZ组血清Cr、BUN、IL-6、TNF-α、IL-10浓度、P-JAK2/JAK2、P-STAT3/STAT3和caspase-3蛋白含量明显升高(P<0.05)，肾小管上皮细胞出现不同程度的肿胀，空泡变性，刷状缘脱落，部分肾小管管腔扩张，肾小管损伤评分和AI明显升高（P<0.05）；与IR组和CPZ组比较，CAP组血清Cr、BUN、IL-6、TNF-α浓度、P-JAK2/JAK2、P-STAT3/STAT3和caspase-3含量明显降低(P<0.05)，肾小管损伤减轻，肾小管损伤评分和AI明显降低（P<0.05），IL-10浓度明显升高（P<0.05）。
结论 辣椒素可减轻缺血-再灌注引起的大鼠肾组织损伤，其机制可能与抑制IL-6/JAK2/STAT3通路，抑制炎症反应，减少细胞凋亡和组织损伤有关。 |
| 英文摘要: |
Objective To investigate the effect and mechanism of capsaicin on renal ischemia-reperfusion injury in rats.
Methods Forty healthy male SD rats weighing 200 - 250 g were randomly divided into 4 groups (n= 10): sham operation group (group S), ischemia-reperfusion group (group IR) ，capsaicin treatment group (group CAP) and both capsazepine and capsaicin treatment group (group CPZ). The renal ischemia-reperfusion injury model was established by clamping bilateral renal pedicle for 45 min and reperfusing for 24 h. Rats in the group CAP and group CPZ were administrated with capsaicin 30mg/kg via intraperitoneal injection 30 min before renal ischemia. Rats in group CPZ were treated with capsazepine 20 mg/kg 15 min prior to administration of capsaicin via intraperitoneal injection．Rats in group S and group IR were administrated with saline. At 24 h after reperfusion, the blood sample was obtained to detect the level of serum concentration of creatinine (Cr), blood urea nitrogen (BUN), tumor necrosis factor-α (TNF-α)，interleukin-6 (IL-6) and interleukin-10 (IL-10)．Renal tissue was obtained to observe the pathological changes (via HE stain), the apoptotic rate (by TUNEL) and expression of Janus kinase 2 (JAK2), signal transducer and activator of transcription 3 (STAT3), phosphorylated Janus kinase 2 (P-JAK2), phosphorylated signal transducer and activator of transcription 3 (P-STAT3) and caspase-3 (with Western blotting).
Results Compared with group S, the levels of Cr, BUN, IL-6, TNF-α, IL-10 and the expression of P-JAK2/JAK2, P-STAT3/STAT3, caspase-3 were increased significantly. Besides, tubule epithelial cells showed drfferent degrees of swelling, vacuolow degeneration, brush margin shelding, part of the tubular cavity diluted, renal tubular damage score and AI were significantly increased in group IR (P < 0.05). Compared with group IR and CPZ, the levels of Cr, BUN, IL-6, TNF-α and the expression of P-JAK2/JAK2, P-STAT3/STAT3, caspase-3 decreased significantly(P < 0.05). Renal tubule inijury allevicated significantly. Renal tubular damage score and AI in group CAP decreased significantly (P < 0.05) and IL-10 increased significantly (P < 0.05).
Conclusion Administration of capsaicin alleviated renal IRI which might attenuate inflammatory responses via IL-6/JAK2/STAT3 signaling pathway． |
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