早期慢性肾病大鼠心脏病变的影响

The Relationship between Anemia and Heart Damages in Early Chronic Kidney Rats

目的:研究早期慢性肾脏疾病(chronic kidney disease,CKD)大鼠心脏病变及其与贫血之间的关系。方法:通过减少肾脏切除量和缩短喂养时间方法建立早期CKD大鼠动物模型,分析其心脏病变及其与贫血之间的关系。结果:(1)实验组大鼠血尿素氮水平、尿白蛋白/肌酐比值、肾小球系膜增生程度均明显高于对照组,但实验组和对照组之间血肌酐水平无明显差异,且病理改变较轻,成功制作早期CKD模型。(2)实验组大鼠心脏/体重比值明显高于对照组(P<0.01),心肌细胞肥大,心肌间质纤维化明显。免疫组化测定显示心肌组织内Ⅰ型和Ⅲ型胶原明显增加。(3)实验组大鼠血红蛋白(Hb)和血细胞压积(Hct)均明显低于对照组,通过单因素相关分析发现心脏重/体重比值、大鼠心脏Ⅰ型胶原阳性面积百分比和Ⅲ型胶原阳性面积百分比均与Hb和Hct呈显著负相关。结论:心脏病变,包括心脏重量明显增加、心肌间质纤维组织增生和胶原增多,存在于早期CKD动物模型中,其严重程度与业已存在的贫血有关。

Object：To analyze the relationship between heart damages and anemia in early chronic kidney disease （CKD） animal model. Methods：By subtotal nephrectomy （70% ± 2.0%） and rats fed for 10 weeks, the early CKD animal model was es tablished. The difference between the experimental group and the control one including urinary albumin/creatinine ratio, serum creatinine （Scr）, blood urea nitrogen （BUN）, hemoglobin （Hb）, hematocrit （Hct）, heart weight/body weight ratio, the pathology of kidney and heart, and collagen Ⅰ and collagen Ⅲ of heart were compared, and the relationship between heart damages and anemia were analyzed further. Results： In our study, the mean percentage of removed kidney was 70.14 ± 2.00%. In experimental group, the main pathological change in kidney was glomerular mesangial proliferation and focal segmental glomerular sclerosis was rare. Compared with the control group, the experimental one had significant higher level of blood urea nitrogen （BUN）, higher value of urinary albumin/creatinine ratio, more severe degree of glomerular mesangial proliferation （P〈0.01）. But there was no obvious difference in serum creatinine （Scr） between the two groups. Compared with the control group, the experimental one had a significant higher value of the heart weight/body weight ratio （P〈0.01） and significant heart pathological changes including myocardial cell hypertrophy and interstitial fibrosis. Immunohistochemistry results showed that collagen Ⅰ and collagen Ⅲ in the myocardial tissue increased significantly in experimental group. Furthermore, Compared with the con trol group, the experimental one had significant lower levels of hemoglobin and hematocrit （P〈0. 01 ）. Linear regression analysis showed that the heart weight/body weight ratio, the percentage of collagen Ⅰ positive area, and the percentage of collagen Ⅲ positive area all had significant negative correlations with hemoglobin（r= -0.91, -0.92, 0.87, respectively, P〈0. 01） and hematocrit （r = -0.89, -0.91, -0.90, respectively, P〈0.01 ）. Conclusion：Heart damages, mainly including heart weight, significant myocardial cell hypertrophy, interstitial fibrosis, and increased levels of collagen Ⅰ and collagen Ⅲ in myocardial tissue, are significantly existed in early CKD animal model. Moreover, it has some definite correlation with the existed anemia.