CAJ | 학술논문

目的：观察氯沙坦对伴血尿酸（SUA）升高的早期慢性肾脏病（CKD）大鼠心脏病变影响并探讨可能机制。方法实验大鼠随机分成A组（假手术组）、B组（ CKD组）、C组（伴SUA升高的CKD组：CKD＋氧嗪酸钾（ OXO））、D组（伴SUA升高的CKD＋氯沙坦组：CKD＋OXO＋氯沙坦），每组15只。采用右肾切除＋OXO连续灌胃法制备SD雄性大鼠伴SUA升高早期CKD模型；OXO剂量为800 mg? kg－1?次－1，每天2次。 D组氯沙坦剂量：20 mg? kg－1?次－1，每天1次。16周后处死大鼠，检测血清肌酐（Scr）、SUA、氧化型低密度脂蛋白（ox－LDL）、超氧化物歧化酶（SOD）；HE和PAS染色观察肾组织病理改变；HE染色观察心脏病理改变，免疫组化法测定心肌I型胶原（ColI）表达情况。结果（1）4组Scr水平无显著差异，C组SUA较其余3组明显升高。与A组相比，其余3组肾组织HE、PAS染色仅有轻微肾小球系膜增生。（2）A组心脏HE染色未见明显形态学改变，心肌ColI少量沉积。 B组心肌细胞间存在少量散在炎症细胞，ColI沉积少量增加。 C组大量炎症细胞浸润，间质充血、纤维化；小血管壁可见成纤维细胞出现；ColI沉积显著增多。 D组病变与C组相似，但程度显著减轻，仅有少量炎症细胞浸润，血管壁偶见炎症细胞，ColI沉积显著减少。统计学分析显示：C组心肌ColI阳性面积百分比较B组显著升高，D组则较C组显著降低。单因素分析发现：大鼠SUA水平与心肌ColI阳性面积百分比呈显著正相关。（3）与B组相比，C组SOD水平显著降低，D组则较C组显著升高；C组ox－LDL较B组明显升高，D组则较C组显著降低。单因素分析发现：SUA、心肌ColI阳性面积百分比均与血清ox－LDL呈显著正相关，与SOD呈显著负相关。多元回归分析显示SUA进入以ColI阳性面积百分比作为应变量的回归方程，所得回归方程为y＝15．410＋0．100x（y＝心肌ColI阳性面积百分比，x＝SUA，15．410为常数）。结论伴SUA升高的早期CKD大鼠存在心脏病理学改变，且病变严重程度与SUA水平呈正相关。氯沙坦可通过降低SUA水平，减轻氧化应激从而保护早期CKD大鼠心脏。目的：觀察氯沙坦對伴血尿痠（SUA）升高的早期慢性腎髒病（CKD）大鼠心髒病變影響併探討可能機製。方法實驗大鼠隨機分成A組（假手術組）、B組（ CKD組）、C組（伴SUA升高的CKD組：CKD＋氧嗪痠鉀（ OXO））、D組（伴SUA升高的CKD＋氯沙坦組：CKD＋OXO＋氯沙坦），每組15隻。採用右腎切除＋OXO連續灌胃法製備SD雄性大鼠伴SUA升高早期CKD模型；OXO劑量為800 mg? kg－1?次－1，每天2次。 D組氯沙坦劑量：20 mg? kg－1?次－1，每天1次。16週後處死大鼠，檢測血清肌酐（Scr）、SUA、氧化型低密度脂蛋白（ox－LDL）、超氧化物歧化酶（SOD）；HE和PAS染色觀察腎組織病理改變；HE染色觀察心髒病理改變，免疫組化法測定心肌I型膠原（ColI）錶達情況。結果（1）4組Scr水平無顯著差異，C組SUA較其餘3組明顯升高。與A組相比，其餘3組腎組織HE、PAS染色僅有輕微腎小毬繫膜增生。（2）A組心髒HE染色未見明顯形態學改變，心肌ColI少量沉積。 B組心肌細胞間存在少量散在炎癥細胞，ColI沉積少量增加。 C組大量炎癥細胞浸潤，間質充血、纖維化；小血管壁可見成纖維細胞齣現；ColI沉積顯著增多。 D組病變與C組相似，但程度顯著減輕，僅有少量炎癥細胞浸潤，血管壁偶見炎癥細胞，ColI沉積顯著減少。統計學分析顯示：C組心肌ColI暘性麵積百分比較B組顯著升高，D組則較C組顯著降低。單因素分析髮現：大鼠SUA水平與心肌ColI暘性麵積百分比呈顯著正相關。（3）與B組相比，C組SOD水平顯著降低，D組則較C組顯著升高；C組ox－LDL較B組明顯升高，D組則較C組顯著降低。單因素分析髮現：SUA、心肌ColI暘性麵積百分比均與血清ox－LDL呈顯著正相關，與SOD呈顯著負相關。多元迴歸分析顯示SUA進入以ColI暘性麵積百分比作為應變量的迴歸方程，所得迴歸方程為y＝15．410＋0．100x（y＝心肌ColI暘性麵積百分比，x＝SUA，15．410為常數）。結論伴SUA升高的早期CKD大鼠存在心髒病理學改變，且病變嚴重程度與SUA水平呈正相關。氯沙坦可通過降低SUA水平，減輕氧化應激從而保護早期CKD大鼠心髒。
목적：관찰록사탄대반혈뇨산（SUA）승고적조기만성신장병（CKD）대서심장병변영향병탐토가능궤제。방법실험대서수궤분성A조（가수술조）、B조（ CKD조）、C조（반SUA승고적CKD조：CKD＋양진산갑（ OXO））、D조（반SUA승고적CKD＋록사탄조：CKD＋OXO＋록사탄），매조15지。채용우신절제＋OXO련속관위법제비SD웅성대서반SUA승고조기CKD모형；OXO제량위800 mg? kg－1?차－1，매천2차。 D조록사탄제량：20 mg? kg－1?차－1，매천1차。16주후처사대서，검측혈청기항（Scr）、SUA、양화형저밀도지단백（ox－LDL）、초양화물기화매（SOD）；HE화PAS염색관찰신조직병리개변；HE염색관찰심장병리개변，면역조화법측정심기I형효원（ColI）표체정황。결과（1）4조Scr수평무현저차이，C조SUA교기여3조명현승고。여A조상비，기여3조신조직HE、PAS염색부유경미신소구계막증생。（2）A조심장HE염색미견명현형태학개변，심기ColI소량침적。 B조심기세포간존재소량산재염증세포，ColI침적소량증가。 C조대량염증세포침윤，간질충혈、섬유화；소혈관벽가견성섬유세포출현；ColI침적현저증다。 D조병변여C조상사，단정도현저감경，부유소량염증세포침윤，혈관벽우견염증세포，ColI침적현저감소。통계학분석현시：C조심기ColI양성면적백분비교B조현저승고，D조칙교C조현저강저。단인소분석발현：대서SUA수평여심기ColI양성면적백분비정현저정상관。（3）여B조상비，C조SOD수평현저강저，D조칙교C조현저승고；C조ox－LDL교B조명현승고，D조칙교C조현저강저。단인소분석발현：SUA、심기ColI양성면적백분비균여혈청ox－LDL정현저정상관，여SOD정현저부상관。다원회귀분석현시SUA진입이ColI양성면적백분비작위응변량적회귀방정，소득회귀방정위y＝15．410＋0．100x（y＝심기ColI양성면적백분비，x＝SUA，15．410위상수）。결론반SUA승고적조기CKD대서존재심장병이학개변，차병변엄중정도여SUA수평정정상관。록사탄가통과강저SUA수평，감경양화응격종이보호조기CKD대서심장。
Objective To observe the influence of losartan on heart disease of early chronic kidney disease ( CKD) rats with elevated serum uric acid ( SUA) and explore the possible mechanism .Methods The experimental rats were divided into group A (sham operation group),group B ( CKD group),group C ( CKD with elevated SUA group,CKD+OXO),group D (CKD with elevated SUA,CKD+OXO+losartan),each of 15 cases.Prepared the male early CKD SD rats with elevated SUA model by right kidney resection and OXO continuous irrigation stomach method ,the dose of OXO was 800 mg/kg/time,2 times/d.The dose of losartan in group D was 20mg/kg/time,1 time/d.All the the rats were killed after 16 weeks.The serum creatinine (Scr),SUA,oxidized low density lipoprotein (ox LDL) and superoxide dismutase (SOD) were detected.The renal pathologic changes were observed by HE and PAS staining ,and the HE staining was used to observe cardiac pathological chan-ges too.The expression of myocardial collagen type I ( ColI) was determinated by immunohistochemical method .Results (1) There were no significant different of Scr between 4 groups.The SUA of group C was higher than that of the other 3 groups. Compared with group A,the other 3 groups had only mild mesangial proliferation in HE、PAS staining of the renal tissue.(2) There was no obvious morphological change in the HE staining of heart in group A ,and there was small amount deposition of myocardial ColI .In group B,a small amount of scattered inflammatory cells was between the myocardial cells .The deposition of myocardial ColI increased a little .A large number of inflammatory cells were infiltrated in group C ,and interstitial hyperemia , fibrosis;the fibroblast appeared in the wall of small vessels;The deposition of myocardial ColI increased significantly .The le-sions of Group D were similar to group C ,But the degree of lesion significantly reduced ,only a small amount of inflammatory cell infiltration ,occasionally seen inflammatory cells in the vascular wall;The deposition of myocardial ColI decreased signifi-cantly.Statistical analysis showed that myocardial ColI positive area percentage in group C was increased significantly compared with group B,and the group D decreased significantly compared with group C .The single factor analysis showed that the SUA level of rats was significant positive correlation with the myocardial ColI positive area percentage .(3) Compared with group B, the SOD level of group C decreased significantly;meanwhile,the group D increased significantly compared with group C .The ox-LDL of group C increased significantly compared with group B ,and the group D decreased significantly compared with group C.The single factor analysis showed that both SUA and myocardial ColI positive area percentage were significant positive corre -lation with serum ox-LDL and significant negative correlation with SOD .The multiple regression analysis showed that ,SUA en-tered the regression equation taking ColI positive area percentage as the dependent variables ,the regression equation was y =15.410+0.100x (y=ColI positive area percentage ,x=SUA,15.410 is a constant).Conclusion The early CKD rats with elevated serum uric acid have cardiac pathology change , and the lesion severity is positively correlated with SUA level .The losartan can reduce oxidative stress in order to protect the early CKD rat heart by reducing the SUA level .