中华肾脏病杂志
中華腎髒病雜誌
중화신장병잡지
2012年
5期
377-382
,共6页
张黎明%唐琦%梅长林%芦怡舟%邬碧波
張黎明%唐琦%梅長林%蘆怡舟%鄔碧波
장려명%당기%매장림%호이주%오벽파
左卡尼汀%慢性肾衰竭%大鼠%心脏
左卡尼汀%慢性腎衰竭%大鼠%心髒
좌잡니정%만성신쇠갈%대서%심장
L-carnitine%Renal failure,chronic%Rats%Myocardium
目的 观察左卡尼汀对慢性肾衰竭大鼠心脏病理变化的影响,并探讨其心脏保护机制.方法 55只雄性SD大鼠按数字随机法分为假手术组(n=10)、模型组(n=15)、左卡尼汀小剂量组(n=10)、中剂量组(n=10)和大剂量组(n=10).除假手术组外,其余各组大鼠行5/6肾切除术.造模后1周,各左卡尼汀组大鼠每日灌胃给药,剂量分别为300、600、900mg/kg.假手术组和模型组则每日予生理盐水灌胃,总疗程17周.观察大鼠24h尿蛋白量、肾功能、超氧化物歧化酶(SOD)、丙二醛( MDA)、白介素6(IL-6)、三磷酸腺苷(ATP)、二磷酸腺苷(ADP)变化.实验结束时,测各组大鼠平均动脉压及心率,并通过心脏超声、全心/体质量比、光镜、透射电镜观察大鼠心脏病理变化.结果 (1)左卡尼汀小、中、大剂量组ATP(μmol/g体质量)(2.35±0.24,3.59±0.28,3.78±0.25)均显著高于模型组(1.61±0.12)(均P＜0.01).(2)心脏超声显示左卡尼汀大剂量组左心室后壁厚度(mm)小于模型组(3.74±0.23比4.18±0.48,P＜ 0.05).(3)左卡尼汀中、大剂量组全心/体质量比值(3.92±0.27,3.65±0.20)均显著低于模型组(3.99±0.27)(P＜ 0.01).(4)光镜下,HE染色显示模型组心肌细胞排列紊乱,心肌细胞肥大；Masson染色显示胶原组织明显增多,部分心肌组织被胶原组织取代,出现心肌间质纤维化.HE染色显示左卡尼汀中、大剂量组心肌细胞排列紊乱；Masson染色显示心肌组织周围胶原纤维增多,心肌间质纤维化,但病变程度和范围均明显减轻.左卡尼汀中、大剂量组心肌病理评分(7.14±1.07,6.13±0.99)均低于模型组(9.88±1.13)(P＜ 0.01).电镜下,模型组可见大片心肌纤维溶解,线粒体增多、肿胀、空泡化,膜断裂、基质加深,为典型的心肌肥厚表现.左卡尼汀治疗组呈剂量依赖性改善病理损害.(5)治疗17周时,左卡尼汀小、中、大剂量组IL-6 (ng/L)(261.86±13.18、240.12±18.70、233.34±36.88比596.64±81.41)和MDA (nmol/L)(15.23±2.01、12.41±0.60、10.97±1.90比21.84±2.71)显著低于模型组；SOD(U/ml)(51.20±6.11、58.51±5.52、60.63±6.94比32.01±5.69)则高于模型组,差异均有统计学意义(均P＜ 0.05).(6)各组大鼠心率差异无统计学意义；模型组和左卡尼汀各组收缩压、舒张压及平均动脉压比较,差异无统计学意义.结论 左卡尼汀可通过改善慢性肾衰竭大鼠的心肌能量代谢、微炎性反应及氧化应激,达到延缓慢性肾衰竭大鼠左心室肥厚、心肌间质纤维化的作用.
目的 觀察左卡尼汀對慢性腎衰竭大鼠心髒病理變化的影響,併探討其心髒保護機製.方法 55隻雄性SD大鼠按數字隨機法分為假手術組(n=10)、模型組(n=15)、左卡尼汀小劑量組(n=10)、中劑量組(n=10)和大劑量組(n=10).除假手術組外,其餘各組大鼠行5/6腎切除術.造模後1週,各左卡尼汀組大鼠每日灌胃給藥,劑量分彆為300、600、900mg/kg.假手術組和模型組則每日予生理鹽水灌胃,總療程17週.觀察大鼠24h尿蛋白量、腎功能、超氧化物歧化酶(SOD)、丙二醛( MDA)、白介素6(IL-6)、三燐痠腺苷(ATP)、二燐痠腺苷(ADP)變化.實驗結束時,測各組大鼠平均動脈壓及心率,併通過心髒超聲、全心/體質量比、光鏡、透射電鏡觀察大鼠心髒病理變化.結果 (1)左卡尼汀小、中、大劑量組ATP(μmol/g體質量)(2.35±0.24,3.59±0.28,3.78±0.25)均顯著高于模型組(1.61±0.12)(均P＜0.01).(2)心髒超聲顯示左卡尼汀大劑量組左心室後壁厚度(mm)小于模型組(3.74±0.23比4.18±0.48,P＜ 0.05).(3)左卡尼汀中、大劑量組全心/體質量比值(3.92±0.27,3.65±0.20)均顯著低于模型組(3.99±0.27)(P＜ 0.01).(4)光鏡下,HE染色顯示模型組心肌細胞排列紊亂,心肌細胞肥大；Masson染色顯示膠原組織明顯增多,部分心肌組織被膠原組織取代,齣現心肌間質纖維化.HE染色顯示左卡尼汀中、大劑量組心肌細胞排列紊亂；Masson染色顯示心肌組織週圍膠原纖維增多,心肌間質纖維化,但病變程度和範圍均明顯減輕.左卡尼汀中、大劑量組心肌病理評分(7.14±1.07,6.13±0.99)均低于模型組(9.88±1.13)(P＜ 0.01).電鏡下,模型組可見大片心肌纖維溶解,線粒體增多、腫脹、空泡化,膜斷裂、基質加深,為典型的心肌肥厚錶現.左卡尼汀治療組呈劑量依賴性改善病理損害.(5)治療17週時,左卡尼汀小、中、大劑量組IL-6 (ng/L)(261.86±13.18、240.12±18.70、233.34±36.88比596.64±81.41)和MDA (nmol/L)(15.23±2.01、12.41±0.60、10.97±1.90比21.84±2.71)顯著低于模型組；SOD(U/ml)(51.20±6.11、58.51±5.52、60.63±6.94比32.01±5.69)則高于模型組,差異均有統計學意義(均P＜ 0.05).(6)各組大鼠心率差異無統計學意義；模型組和左卡尼汀各組收縮壓、舒張壓及平均動脈壓比較,差異無統計學意義.結論 左卡尼汀可通過改善慢性腎衰竭大鼠的心肌能量代謝、微炎性反應及氧化應激,達到延緩慢性腎衰竭大鼠左心室肥厚、心肌間質纖維化的作用.
목적 관찰좌잡니정대만성신쇠갈대서심장병리변화적영향,병탐토기심장보호궤제.방법 55지웅성SD대서안수자수궤법분위가수술조(n=10)、모형조(n=15)、좌잡니정소제량조(n=10)、중제량조(n=10)화대제량조(n=10).제가수술조외,기여각조대서행5/6신절제술.조모후1주,각좌잡니정조대서매일관위급약,제량분별위300、600、900mg/kg.가수술조화모형조칙매일여생리염수관위,총료정17주.관찰대서24h뇨단백량、신공능、초양화물기화매(SOD)、병이철( MDA)、백개소6(IL-6)、삼린산선감(ATP)、이린산선감(ADP)변화.실험결속시,측각조대서평균동맥압급심솔,병통과심장초성、전심/체질량비、광경、투사전경관찰대서심장병리변화.결과 (1)좌잡니정소、중、대제량조ATP(μmol/g체질량)(2.35±0.24,3.59±0.28,3.78±0.25)균현저고우모형조(1.61±0.12)(균P＜0.01).(2)심장초성현시좌잡니정대제량조좌심실후벽후도(mm)소우모형조(3.74±0.23비4.18±0.48,P＜ 0.05).(3)좌잡니정중、대제량조전심/체질량비치(3.92±0.27,3.65±0.20)균현저저우모형조(3.99±0.27)(P＜ 0.01).(4)광경하,HE염색현시모형조심기세포배렬문란,심기세포비대；Masson염색현시효원조직명현증다,부분심기조직피효원조직취대,출현심기간질섬유화.HE염색현시좌잡니정중、대제량조심기세포배렬문란；Masson염색현시심기조직주위효원섬유증다,심기간질섬유화,단병변정도화범위균명현감경.좌잡니정중、대제량조심기병리평분(7.14±1.07,6.13±0.99)균저우모형조(9.88±1.13)(P＜ 0.01).전경하,모형조가견대편심기섬유용해,선립체증다、종창、공포화,막단렬、기질가심,위전형적심기비후표현.좌잡니정치료조정제량의뢰성개선병리손해.(5)치료17주시,좌잡니정소、중、대제량조IL-6 (ng/L)(261.86±13.18、240.12±18.70、233.34±36.88비596.64±81.41)화MDA (nmol/L)(15.23±2.01、12.41±0.60、10.97±1.90비21.84±2.71)현저저우모형조；SOD(U/ml)(51.20±6.11、58.51±5.52、60.63±6.94비32.01±5.69)칙고우모형조,차이균유통계학의의(균P＜ 0.05).(6)각조대서심솔차이무통계학의의；모형조화좌잡니정각조수축압、서장압급평균동맥압비교,차이무통계학의의.결론 좌잡니정가통과개선만성신쇠갈대서적심기능량대사、미염성반응급양화응격,체도연완만성신쇠갈대서좌심실비후、심기간질섬유화적작용.
Objective To investigate the effect of L-carnitine on pathological changes of myocardium and the underlying mechanism in chronic renal failure rats (CRF). Methods A total of 55 male SD rats were randomly divided into sham group (n=10),model group (n=15),low dose (300 mg/kg),medium dose (600 mg/kg) and high dose (900 mg/kg) L-carnitine group(n=10,each).5/6 subtotal nephrectomy was performed in these rats without sham group.One week after the operation,normal saline or corresponding dose L-carnitine were intragastrically administrated to sham and model group or L-carnitine groups for 17 weeks.Transthoracic echocardiography,mean arterial pressure (MAP),heart rate (HR) and heart weight/body weight were assessed.Moreover,24h urine protein,renal function,SOD,MDA,IL-6,ATP,ADP were measured at the end of the study.Additionally,pathological changes in myocardium were detected by light microscope and transmission electron microscope. Results (1) ATP (μmol/g·wt)in L-carnitine groups (2.35±0.24,3.59±0.28,3.78±0.25) was significantly higher than that in model group (1.61±0.12) (all P＜0.01).(2) Thickness of posterior wall of left ventricle (mm) in high dose L-carnitine group was thinner than that in model group (3.74±0.23 vs 4.18±0.48,P＜0.05). (3) The ratios of heart weight to body weight in both medium dose and high dose L-carnitine groups (3.92±0.27,3.65±0.2) were significantly lower compared to model group (3.99±0.27) (all P＜0.01). (4) Under light microscopy,disarrangement and hypertrophy of cardiac myocytes,increased myocardial fibrosis were observed in model group, while these changes and the pathological scores were significantly improved in both medium dose and high dose L-carnitine groups (7.14±1.07,6.13±0.99),as compared with model group (9.88±1.13) (all P＜0.01).Under electron microscopy,typical changes in cardiac hypertrophy were observed,including dissolution of myocardial fibers,increasing and swelling of mitochondria,membrane rupture as well as matrix increase in model group,while these changes were ameliorated by L-carnitine in a dose-dependent manner. (5) Seventeen weeks after the treatment,both IL-6 and MDA were decreased in all L-carnitine-treated groups than those in model group [IL-6 (ng/L):261.86±13.18,240.12±18.7,233.34±36.88 vs 596.64±81.41; MDA (nmol/L):15.23±2.01,12.41±0.6.10.97±1.9 vs 21.84±2.71).Whereas,SOD (U/ml) were increased in L-carnitine-treated groups (51.2±6.11,58.51±5.52,60.63±6.94) than that in model group(32.01 ±5.69 )(all P＜0.05).(6) No significant differences of systolic,diastolic blood pressure or MAP were found among groups. Conclusion L-carnitine can improve energy metabolism,micro-inflammation and oxidative stress in myocardium of CRF rats,which may be associated with the amelioration of cardiac hypertrophy and fibrosis.
