CAJ | 학술논문

目的观察曲美他嗪(TZM)对慢性肾衰竭大鼠心肌能量代谢及病理结构的影响。方法 40只雄性SD大鼠行5/6肾切除术，将成模大鼠随机分为手术对照组、曲美他嗪小剂量(3 mg/kg)组、中剂量(6 mg/kg)组和大剂量(9 mg/kg)组，并设假手术组(雄性SD大鼠10只)。各治疗组大鼠每日灌胃给药，假手术组和手术对照组则予生理盐水，持续17周。实验结束时，测量各组大鼠左心室/体质量、全心/体质量比值；监测平均动脉压及心率；观察心脏超声检查和病理形态学改变，并测定尿素氮(BUN)、血肌酐(Scr)、三磷酸腺苷(ATP)、二磷酸腺苷(ADP)、超氧化物歧化酶(SOD)、丙二醛(MDA)、白细胞介素6(IL-6)、肿瘤坏死因子(TNF)α。结果 (1)曲美他嗪中剂量组、大剂量组左室收缩末内径、左室舒张末期前壁厚度、左室收缩末期前壁厚度、左室舒张末期后壁厚度均显著低于手术对照组(均P＜ 0.05)。(2)曲美他嗪中剂量组、大剂量组左心室/体质量、全心/体质量均显著低于手术对照组(P＜0.05)。(3)光镜可见手术对照组心肌细胞排列紊乱、肥大，部分心肌纤维化；电镜可见手术对照组心肌组织大片心肌纤维溶解，线粒体增多、肿胀、空泡化，膜断裂。各治疗组心肌病理形态学改变均比手术对照组轻，且随曲美他嗪剂量增大有好转趋势。(4)各组大鼠心率差异无统计学意义，5/6肾切除各组收缩压、舒张压及平均动脉压均显著高于假手术组(P＜0.01)，而5/6肾切除各组间收缩压、舒张压及平均动脉压差异均无统计学意义(P＞0.05)。(5)曲美他嗪3个剂量组ATP、ADP均显著高于手术对照组(均P＜0.05)，且大剂量组、中剂量组ATP、ADP均显著高于小剂量组(均P＜ 0.05)。(6)曲美他嗪大剂量组、中剂量组剂量IL-6、TNF-α、MDA均显著低于手术对照组(均P＜ 0.05)，而SOD均显著高于手术对照组(均P＜0.05)。结论曲美他嗪可以改善慢性肾衰竭大鼠心肌能量代谢、微炎性反应和氧化应激状态，从而防治慢性肾衰竭大鼠心肌细胞纤维化及左心室肥厚。目的觀察麯美他嗪(TZM)對慢性腎衰竭大鼠心肌能量代謝及病理結構的影響。方法 40隻雄性SD大鼠行5/6腎切除術，將成模大鼠隨機分為手術對照組、麯美他嗪小劑量(3 mg/kg)組、中劑量(6 mg/kg)組和大劑量(9 mg/kg)組，併設假手術組(雄性SD大鼠10隻)。各治療組大鼠每日灌胃給藥，假手術組和手術對照組則予生理鹽水，持續17週。實驗結束時，測量各組大鼠左心室/體質量、全心/體質量比值；鑑測平均動脈壓及心率；觀察心髒超聲檢查和病理形態學改變，併測定尿素氮(BUN)、血肌酐(Scr)、三燐痠腺苷(ATP)、二燐痠腺苷(ADP)、超氧化物歧化酶(SOD)、丙二醛(MDA)、白細胞介素6(IL-6)、腫瘤壞死因子(TNF)α。結果 (1)麯美他嗪中劑量組、大劑量組左室收縮末內徑、左室舒張末期前壁厚度、左室收縮末期前壁厚度、左室舒張末期後壁厚度均顯著低于手術對照組(均P＜ 0.05)。(2)麯美他嗪中劑量組、大劑量組左心室/體質量、全心/體質量均顯著低于手術對照組(P＜0.05)。(3)光鏡可見手術對照組心肌細胞排列紊亂、肥大，部分心肌纖維化；電鏡可見手術對照組心肌組織大片心肌纖維溶解，線粒體增多、腫脹、空泡化，膜斷裂。各治療組心肌病理形態學改變均比手術對照組輕，且隨麯美他嗪劑量增大有好轉趨勢。(4)各組大鼠心率差異無統計學意義，5/6腎切除各組收縮壓、舒張壓及平均動脈壓均顯著高于假手術組(P＜0.01)，而5/6腎切除各組間收縮壓、舒張壓及平均動脈壓差異均無統計學意義(P＞0.05)。(5)麯美他嗪3箇劑量組ATP、ADP均顯著高于手術對照組(均P＜0.05)，且大劑量組、中劑量組ATP、ADP均顯著高于小劑量組(均P＜ 0.05)。(6)麯美他嗪大劑量組、中劑量組劑量IL-6、TNF-α、MDA均顯著低于手術對照組(均P＜ 0.05)，而SOD均顯著高于手術對照組(均P＜0.05)。結論麯美他嗪可以改善慢性腎衰竭大鼠心肌能量代謝、微炎性反應和氧化應激狀態，從而防治慢性腎衰竭大鼠心肌細胞纖維化及左心室肥厚。
목적 관찰곡미타진(TZM)대만성신쇠갈대서심기능량대사급병리결구적영향。방법 40지웅성SD대서행5/6신절제술，장성모대서수궤분위수술대조조、곡미타진소제량(3 mg/kg)조、중제량(6 mg/kg)조화대제량(9 mg/kg)조，병설가수술조(웅성SD대서10지)。각치료조대서매일관위급약，가수술조화수술대조조칙여생리염수，지속17주。실험결속시，측량각조대서좌심실/체질량、전심/체질량비치；감측평균동맥압급심솔；관찰심장초성검사화병리형태학개변，병측정뇨소담(BUN)、혈기항(Scr)、삼린산선감(ATP)、이린산선감(ADP)、초양화물기화매(SOD)、병이철(MDA)、백세포개소6(IL-6)、종류배사인자(TNF)α。결과 (1)곡미타진중제량조、대제량조좌실수축말내경、좌실서장말기전벽후도、좌실수축말기전벽후도、좌실서장말기후벽후도균현저저우수술대조조(균P＜ 0.05)。(2)곡미타진중제량조、대제량조좌심실/체질량、전심/체질량균현저저우수술대조조(P＜0.05)。(3)광경가견수술대조조심기세포배렬문란、비대，부분심기섬유화；전경가견수술대조조심기조직대편심기섬유용해，선립체증다、종창、공포화，막단렬。각치료조심기병리형태학개변균비수술대조조경，차수곡미타진제량증대유호전추세。(4)각조대서심솔차이무통계학의의，5/6신절제각조수축압、서장압급평균동맥압균현저고우가수술조(P＜0.01)，이5/6신절제각조간수축압、서장압급평균동맥압차이균무통계학의의(P＞0.05)。(5)곡미타진3개제량조ATP、ADP균현저고우수술대조조(균P＜0.05)，차대제량조、중제량조ATP、ADP균현저고우소제량조(균P＜ 0.05)。(6)곡미타진대제량조、중제량조제량IL-6、TNF-α、MDA균현저저우수술대조조(균P＜ 0.05)，이SOD균현저고우수술대조조(균P＜0.05)。결론곡미타진가이개선만성신쇠갈대서심기능량대사、미염성반응화양화응격상태，종이방치만성신쇠갈대서심기세포섬유화급좌심실비후。
Objective To determine the effects of trimetazidine (TMZ) on pathology and energy metabolism of myocardium in chronic renal failure (CRF) rats. Methods CRF models were built in Sprague-Dawley (SD) rats with 5/6 subtotal nephrectomy, and animals were randomyly divided into sham group, control group and three groups treated with different doses of TMZ (3 mg/kg,6 mg/kg or 9 mg/kg).TMZ was intragastrically administrated to CRF rats for 17 weeks, while physiological saline was used as control. Transthoracic echocardiography was performed and myocardial morphosis was observed.Left ventricular weight/body weight (LVW/BW) and heart weight/body weight (HW/BW) were measured, and heart rate, and mean arterial pressure (MAP)were detected at the end of the study, while several parameters were detected, including urea nitrogen (BUN), creatinine (Scr), triphosaden (ATP), adenosine diphosphate (ADP), superoxide dismutase (SOD), malondialdehyde (MDA), interleukin 6 (IL-6) and tumor necrosis factor α (TNF-α).Results (l)Left ventricle end-systolic dimensions, anterior wall end-diastolic and end-systolic thicknesses, and posterior wall end-diastolic thickness were significantly lower in rats treated with either medium dose or high dose of TMZ, as compared with control group (P＜0.05).(2)LVW/BW and HW/BW in rats treated with either medium dose or high dose of TMZ were significantly lower than those in control group (P＜0.05). (3)Various pathological changes were observed in control group, such as irregular arrangement and hypertrophy of the cardiomyocytes, myocardial fibrosis,mitochondrial swelling, focal muscle fiber dissolution, etc.However, all these pathological changes were apparently ameliorated in TMZ-treated groups, while the beneficial effects of TMZ therapy were dose-dependent. (4)No difference was observed in heart rate among all the groups.Although no difference existed in all the CRF rats, concerning on the systolic/diastolic blood pressure and mean arterial pressure (P＞0.05), these parameters were elevated in CRF rats, as compared with sham-operated group (P＜0.01). (5)ATP and ADP in TMZ-treated rats were significantly higher as compared with control (P＜0.05), moreover, medium dose and high dose of TMZ were superior to low dose (P＜0.05).(6)SOD was significantly increased in TMZ-treated rats (P＜0.05), while IL-6,TNF-α and MDA were significantly decreased in medium dose and high dose of TMZ, as compared with control (P＜0.05). Conclusion TMZ may prevent myocardial fibrosis and left ventricular hypertrophy in chronic renal failure via ameliorating myocardial energy metabolism and alleviating inflammatory reaction and oxidative stress.