基础医学与临床 ›› 2021, Vol. 41 ›› Issue (2): 197-202.

• 研究论文 • 上一篇    下一篇

慢性肾脏病血管钙化大鼠并发心肌炎性反应

袁玲1, 聂卫1, 王蕾2, 王宏2, 崔晓雪1, 刘琳娜3*   

  1. 天津市医药科学研究所 1.病理室; 2.心脑血管药物研发中心, 天津 300020;
    3.中山市中医院 肾内科, 广东 中山 528401
  • 收稿日期:2019-12-12 修回日期:2020-05-25 出版日期:2021-02-05 发布日期:2021-01-19
  • 通讯作者: *1128sun@163.com
  • 基金资助:
    天津市卫生和计划生育委员会中医中西医结合科研项目(2017082);广东省中医药局科研项目(20182166)

Myocardial inflammatory response in rats with vascular calcification caused by chronic kidney disease

YUAN Ling1, NIE Wei1, WANG Lei2, WANG Hong2, CUI Xiao-xue1, LIU Lin-na3*   

  1. 1. Department of Pathology; 2. Cardiovascular and Cerebrovascular Medicine Research and Development Center,Tianjin Institute of Medical Science; Tianjin 300020;
    3. Department of Nephrology, Zhongshan Hospital of Traditional Chinese Medicine, Zhongshan 528401, China
  • Received:2019-12-12 Revised:2020-05-25 Online:2021-02-05 Published:2021-01-19
  • Contact: *1128sun@163.com

摘要: 目的 观察慢性肾脏病血管钙化(CKD-VC)大鼠并发的心肌炎性损害及相关炎性因子TLR4、IL-6和TNF-α的表达。方法 将大鼠分为对照组和CKD-VC组(腺嘌呤200 mg/kg灌胃+高磷0.5 g/d饮水)。5 周末检测血常规及心、肾和主动脉组织学改变。10 周末留取大鼠血清,检测肌酐(Scr)、尿素氮(BUN)、钙(Ca)和磷(P);取心脏、肾脏和主动脉,常规病理检查观察组织学改变;von Kossa染色鉴定血管钙化灶;Masson染色检测肾纤维化;免疫组织化学法检测心脏组织TLR4、IL-6、TNF-α的表达。结果 随CKD肾脏病变进展,并发心脏炎性病变逐渐明显,5 周时CKD-VC组血嗜酸性粒细胞和中性粒细胞均较对照组明显升高(P<0.01),1只动物心肌见少量淋巴细胞浸润;主动脉经von Kossa染色未观察到血管钙化发生。至 10 周时,心脏出现多发的心肌细胞坏死灶伴炎细胞浸润,炎性区域TLR4、IL-6和TNF-α均呈阳性表达;经von Kossa染色鉴定的血管钙化在CKD-VC组发生率为5/7。结论 腺嘌呤灌胃联合高磷饮水诱导CKD肾损害和血管钙化的同时激活了TLR4、TNF-α和IL-6等炎性因子的表达,造成了心肌慢性炎性损害。

关键词: 慢性肾脏病, 腺嘌呤, 心血管疾病, 血管钙化, 心肌炎性反应

Abstract: Objective To observe the myocardial inflammatory response and the expression of TLR4, IL-6 and TNF-α in rats with chronic kidney disease vascular calcification (CKD-VC). Methods Rats were divided into control group and CKD-VC group(adenine 200 mg/kg gavage+ high phosphorus 0.5 g/d drinking water). Blood routine and histological changes of heart, kidney and aorta were detected at 5 weeks. At 10 weeks, the serum of rats was collected to detect creatinine (Scr), urea nitrogen (BUN), serum calcium (Ca) and serum phosphorus (P); heart, kidney and aorta were taken, and histopathology change was observed by routine pathological examination; von Kossa staining to identify vascular calcification; Masson staining to detect renal fibrosis; immunohistochemistry to detect TLR4, IL-6 and TNF-α expression changes. Results As the CKD kidney disease progressed, the inflammatory lesions of the heart became more and more obvious. At 5th week, the counting of peripheral eosinophils and neutrophils in CKD-VC group was significantly higher than the control group (both P<0.01), a small amount of lymphocytes infiltrated in one animal's myocardium; No vascular calcification was observed in the aorta by von Kossa staining. At 10th week, there were multiple myocardial necrosis in the heart with inflammatory cell infiltration, and TLR4, IL-6 and TNF-α were positive in the inflammation area; the incidence rate of vascular calcification identified by von Kossa staining in the CKD-VC group was 5/7. Conclusions Adenine gavage combined with the drinking water of high phosphate level induces CKD renal damage and vascular calcification, which simultaneously activates the expression of inflammatory factors such as TLR4, TNF-α and IL-6, causing chronic inflammatory damage of myocardium.

Key words: chronic kidney disease, adenine, cardiovascular disease, vascular calcification, myocardial inflammatory response

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