Effect of exercise and adrenal insufficiency on urea production in rats

Experiments on Wistar rats were designed to study the effect of exercise on urea production in the liver of intact and adrenalectomized rats. The urea production rate was assessed by the¹⁴C-urea content in liver tissue after administration of NaH¹⁴CO₃. In intact rats swimming caused increases in¹⁴C-urea content in the liver compared to the resting concentrations in intact control rats: by 45% after 30 min of swimming carrying an additional load of 10% body mass by, 35% after 3 h of swimming without an additional load and by 103% after 10 h of swimming. Concentrations of urea in liver and blood were elevated simultaneously. The specific activity of¹⁴C-urea did not change significantly as a result of the exercise performed. In adrenalectomized rats the basal rate of urea production was reduced by an insignificant amount, but swimming for 3 h resulted in a decrease in liver¹⁴C-urea (by 24%). The results confirmed the exercise-induced increase in urea production and indicated as essential role for adrenal hormones in this response.     

Effects of mineralocorticoids on Na+ and K+ excretion in the adrenalectomized rat

The short-term effects (within 4 h) of low doses of intravenous aldosterone or deoxycorticosterone on potassium and sodium urinary excretion were studied by clearance techniques in 24-h adrenalectomized, anesthetized male rats. All animals were substituted with a glucocorticoid (dexamethasone; plasma concentration approximately 6 nM) to maintain normal glomerular filtration rate. The mineralocorticoid effects were studied under various conditions of sodium and potassium load. Mineralocorticoid administration uniformly resulted in antinatriuresis, starting within 30-60 min and, at the peak effect, amounting to 1-2% sodium fractional excretion. The level of antinatriuresis was directly related to the control sodium excretion before aldosterone administration. Mineralocorticoids induced a significant kaliuresis in all groups except one, the one receiving the lowest sodium load. The aldosterone-induced kaliuresis was also related to the sodium load and the control fractional sodium excretion level and was simultaneous with the beginning of the reduced sodium excretion. In control, mineralocorticoid-deprived rats, kaliuresis was not enhanced by increasing the sodium load. Control as well as mineralocorticoid-treated rats responded by an increased kaliuresis following an acute potassium load and by a decreased kaliuresis after 3 days of low potassium diet.     

Urinary N-acetyl-beta-D-glucosaminidase and malondialdehyde as a markers of renal damage in burned patients

This study was aimed to evaluate renal dysfunction during three weeks after the burn injuries in 12 patients admitted to the Hallym University Hankang Medical Center with flame burn injuries (total body surface area, 20-40%). Parameters assessed included 24-hr urine volume, blood urea nitrogen, serum creatinine, creatinine clearance, total urinary protein, urinary microalbumin, 24-hr urinary N-acetyl-beta-D-glucosaminidase (NAG) activity, and urinary malondialdehyde (MDA). Statistical analysis was performed using repeated measures ANOVA test. The 24-hr urine volume, creatinine clearance, and urinary protein significantly increased on day 3 post-burn and fell thereafter. The urine microalbumin excretion showed two peak levels on day 0 post-burn and day 3. The 24-hr urinary NAG activity significantly increased to its maximal level on day 7 post-burn and gradually fell thereafter. The urinary MDA progressively increased during 3 weeks after the burn injury. Despite recovery of general renal function through an intensive care of burn injury, renal tubular damage and lipid peroxidation of the renal tissue suggested to persist during three weeks after the burn. Therefore, a close monitoring and intensive management of renal dysfunction is necessary to prevent burn-induced acute renal failure as well as to lower mortality in patients with major burns.     

Renal function and endocrine responses to arm exercise in euhydrated individuals with spinal cord injury

This study investigated the renal and endocrine responses to arm exercise in persons with spinal cord injury (SCI) under euhydration conditions (ad libitum drinking of water) and determined the physiological effects of exercise on renal function in these subjects. Eleven SCI (spinal lesions between T6 and L1, American Spinal Injury Association impairment scale A) and 14 able-bodied (AB) persons first rested for 1 h in a sitting position, before undergoing 2-h arm-crank ergometer exercise at 60% of maximum oxygen consumption followed by a 2-h recovery period. On another day, all subjects participated in a time control study (5 h of rest condition in sitting position). Urine and blood samples were collected hourly. There were no differences in mean blood pressure between the two groups. SCI patients showed attenuated increase in plasma adrenaline and increase in plasma aldosterone compared with AB controls, but similar changes in human atrial natriuretic polypeptide, plasma renin activity and plasma antidiuretic hormone following the exercise. Creatinine clearance, osmolal clearance, free water clearance and fractional excretion of Na⁺ did not change during exercise in any of the subjects. These findings suggested that activated aldosterone and attenuated adrenaline responses during exercise in SCI could be due to adaptation to disordered sympathetic nervous system triggered to maintain renal function. The results showed no exercise-related adverse effects on renal function in hydrated subjects with SCI.     

The excretion of urea by dogs following a meat meal.

1. After a meal of meat (10g/kg), urea excretion in dogs increased by about 200%, plasma urea by 60% and exogenous creatinine clearance by 40% in comparison with control experiments. 2. Urea, given by stomach tube in doses producing the same increase in plasma urea, caused urea excretion to increase by only 90%, with no increase in creatinine clearance. With the increased glomerular filtration rate after meat there was added excretion of urea. 3. In control experiments and after urea, the rate of excretion of urea was directly proportional to plasma urea. The ratio urea clearance/creatinine clearance, was 0-45. 4. After meat, urea clearance increased more than creatinine clearance, the ratio increasing to 0-55, i.e. a smaller fraction of the filtered urea was re-absorbed after meat. 5. After meat, 10g/kg, the rate of urea production rose to 230-600 mumole/min for 4-6 hr.     

Effects of high-intensity intermittent swimming on PGC-1alpha protein expression in rat skeletal muscle

AIM: The aim of the present investigation was to elucidate the effects of exercise intensity on exercise-induced expression of peroxisome proliferator-activated receptor gamma coactivator-1alpha (PGC-1alpha) protein in rat skeletal muscle. METHODS: We measured PGC-1alpha content in the skeletal muscles of male Sprague-Dawley rats (age: 5-6 weeks old; body weight: 150-170 g) after a single session of high-intensity intermittent exercise (HIE) or low-intensity prolonged swimming exercise (LIE). During HIE, the rats swam for fourteen 20-s periods carrying a weight (14% of body weight), and the periods of swimming were separated by a 10-s pause. LIE rats swam with no load for 6 h in two 3-h sessions, separated by 45 min of rest. RESULTS: After HIE, the PGC-1alpha protein content in rat epitrochlearis muscle had increased by 126, 140 and 126% at 2, 6 and 18 h, respectively, compared with that of the age-matched sedentary control rats' muscle. Immediately, 6 and 18-h after LIE, the PGC-1alpha protein content in the muscle was significantly elevated by 84, 95 and 67% respectively. The PGC-1alpha protein content observed 6 h after HIE tended to be higher than that observed after LIE. However, there was no statistically significant difference between the two values (P = 0.12). CONCLUSION: The present investigation suggests that irrespective of the intensity of the exercise, PGC-1alpha protein content in rat skeletal muscle increases to a comparable level when stimuli induced by different protocols are saturated. Further, HIE is a potent stimulus for enhancing the expression of PGC-1alpha protein, which may induce mitochondrial biogenesis in exercise-activated skeletal muscle.     

低氧性肾间质纤维化和游泳运动对大鼠尾加压素Ⅱ及其受体表达的影响

目的: 探讨慢性低氧性肾纤维化大鼠尾加压素Ⅱ(UⅡ)及其受体(GPR14)的变化,以及游泳运动在其中的作用。方法: 45只雄性SD大鼠随机分成3组,即对照组、低氧组(低氧7周)和游泳组(低氧+游泳锻炼7周组,即低氧3周后,每天1 h无负重游泳4周)。测定血清肌酐(Scr)、血尿素氮(BUN)和血桨UⅡ含量,以及肾组织羟脯氨酸(Hyp)含量、UⅡ及GPR14 mRNA表达和UⅡ蛋白表达。结果: (1)Scr和BUN含量:低氧组较对照组分别低18.5%和14.1%(均P< 0.05),而游泳组与低氧组间无显著差别;(2)肾组织Hyp含量:低氧组较对照组高42.9%(P<0.01),而游泳组较低氧组低26.1%(均P<0.05);(3)血浆UⅡ含量:低氧组较对照组高380.8%(P<0.01),而游泳组较低氧组低42.6%(P<0.01);(4)肾组织UⅡ mRNA表达:低氧组较对照组上调104.5%,游泳组较低氧组下调33.2%(均P<0.01);GPR14 mRNA表达:低氧组较对照组上调35.4%(P<0.01),而游泳组与低氧组间无显著差异;(5)肾组织UII蛋白的表达:低氧组明显高于对照组(P<0.01),而游泳组低于低氧组(P<0.01);(6)van Gieson染色显示低氧组肾血管胶原纤维增生明显,而游泳组明显改善。结论: 慢性低氧性肾纤维化大鼠尾加压素Ⅱ及其受体的表达上调;适度游泳运动有减轻慢性低氧肾间质纤维化的作用,并下调尾加压素Ⅱ基因与蛋白的表达。     

Phosphate and cyclic AMP excretion decreases during less than 12 hours of hypoxia in conscious rats

Hypocapnia is known to have an antiphosphaturic effect that overcomes the phosphaturic effect of hypoxia. The objective of this study was to examine whether conscious rats exposed to acute hypoxia show a decrease in phosphate excretion due to the concomitant hypocapnia. Wistar rats weighing 200 g were exposed to hypoxia (inspired oxygen fraction=0.10) or normoxia (inspired oxygen fraction=0.21) for 6 h; and rats were alternately exposed to hypoxia or normoxia every 12 h for a total 36 h. Renal clearance and hormone studies were performed. Rats exposed to 6 h of hypoxia (n = 11) showed significant hypophosphaturia and decreases in absolute and fractional excretion of phosphate (0.38±0.10 μg min^-1, mean ±SE, P<0.0001 and 0.59±0.15%, P<0.0001) as compared with normoxic rats (n = 11, 3.91±0.68 μg min-¹ and 5.62±0.85%). In addition, nephrogenous adenosine 3′,5′-cyclic monophosphate level per glomerular filtrate was significantly decreased (-0.87±0.64 nmol dL GF^-1, P<0.05) and plasma parathyroid hormone level was unchanged (45.2±9.5 pg mL-¹) after 6 h of hypoxia as compared with normoxic rats (4.03±1.83 nmol dL GF-¹ and 54.3±10.4 pg mL-¹). A parallel increase in urinary noradrenaline and a decrease in dopamine excretion was observed in rats after 6 h of hypoxia. The decreased phosphate and adenosine 3′,5′-cyclic monophosphate excretion during acute hypoxia were restored to normoxic levels by reoxygenation with 21% oxygen in the study of 12-h intermittent hypoxia. In summary, (1) hypoxia produced by inhalation of 10% oxygen for 12 h or less causes reduced phosphate and adenosine 3′,5′-cyclic monophosphate (cAMP) excretion by spontaneously breathing rats; (2) these effects are reversed by reoxygenation and (3) hypoxia elicits a parallel increase in noradrenaline excretion and a decrease in dopamine excretion. These data suggest that renal adrenergic and dopaminergic systems play important roles in hypophosphaturia during acute hypoxia in conscious rats.     

Concentration and dilution of the urine in partially hepatectomized,conscious rats

1. The influence of partial hepatectomy on urinary concentrating ability and renal tissue sodium was determined in conscious rats deprived of water for 24 h. In comparison with a sham operation, partial hepatectomy resulted in: a) a 50% reduction in free-water reabsorption, urinary osmolality, and osmolal urine-to-plasma ratio; b) depression of free-water reabsorption at similar levels of osmolal clearance above 200 microliter/min per ml of GFR during the infusion of hypertonic NaCl and vasopressin; and c) a 30% reduction in sodium content of the renal papilla and outer medulla. 2. The renal response to an intravenous water load (2.5% glucose infused to 2.5% of body wt at 0.4 ml/min) was determined in sham-operated and partially hepatectomized, conscious rats. By 60 min after the water load, both groups had excreted practically all of the load. However, during and for 30 min after the infusion in the partially hepatectomized group, the percent of the water load excreted, urine flow, and free-water clearance were significantly reduced while urinary osmolality and osmolal urine-to-plasma ratio were significantly elevated. 3. These experiments demonstrate that shortly after partial removal of the liver the renal concentrating ability is defective and the excretion of a water load is not grossly impaired.     

Prevention of exercise-induced cardiac hypertrophy in rats by chemical sympathectomy (guanethidine treatment)

The effect of 'chemical sympathectomy', produced by daily intraperitoneal injections of guanethidine sulphate for six weeks, was studied in sedentary rats and in rats chronically exercised by swimming. The guanethidine-treatment itself caused the following changes. There was a reduction in the rate of weight gain resulting in a 7% lower final body weight. Organ content of noradrenaline was decreased by 90% in spleen and submandibular glands and by 83% in the heart. Urinary excretion of noradrenaline was also decreased, but to a lesser degree, both during rest (45% lower) and after acute exercise (46% lower), while the urinary excretion of adrenaline was no different from that of controls. There was a compensatory adrenal hypertrophy in the guanethidine-treated rats, with a significant increase in adrenal catecholamine levels that was more pronounced for noradrenaline (+45%) than for adrenaline (+11%). Chronic physical exercise produced the expected degree of cardiac hypertrophy in untreated rats, but this adaptive cardiac hypertrophy was completely absent in the exercised guanethidine-treated rats. The results indicate, firstly that a good degree of chemical sympathectomy was obtained and that the persistence of a considerable urinary excretion of catecholamines in the guanethidine-treated rats was due to a compensatory increase in the secretory activity of the adrenal medulla. Secondly, it is suggested that the adaptive cardiac hypertrophy produced by chronic exercise is not caused by a direct effect of the increased work load on the cardiac muscle cell, but is instead mediated by release of a trophic factor from cardiac sympathetic nerves, probably noradrenaline itself but possibly a secretory protein.     

Metoprine-induced thirst and diuresis in Wistar rats

In the present study, the renal responses to metoprine, a histamine-N-methyltransferase inhibitor, were studied in conscious rats. Metoprine (10-20 mg kg(-1)) or vehicle were administered i.p. to male Wistar rats and the effects were followed for the subsequent 24 h. It was found that as early as 3 h after the drug administration metoprine 20 mg kg(-1) had increased water consumption and urine flow approximately 6-8-fold. The treatment decreased urine osmolality and increased free water clearance, but caused no change in plasma renin activity or plasma vasopressin concentration. In addition, a metoprine-induced elevation in the systolic blood pressure was observed during the first few hours of the experiment. During the nocturnal period of the study, glomerular filtration rate and the excretion of electrolytes did not increase in metoprine-treated rats as they did in control rats. A decrease in the release of atrial natriuretic peptide was also found. The present results show that inhibition of histamine catabolism by metoprine causes massive changes in renal functions. It seems to promote water excretion by the kidneys but, on the other hand, to reduce the excretion of electrolytes. Although the exact mechanisms, especially the role of increased blood pressure and nocturnal suppression of atrial natriuretic peptide, require further clarification, the present data suggest that renin-angiotensin system and vasopressin were not involved in these renal responses to metoprine.     

Serum beta2-microglobulin in cadmium exposed workers.

In cadmium exposed workers with renal tubular dysfunction the determination of beta2m in urine is an important diagnostic test. Cadmium exposure's influence on serum beta2m levels and its relationship to urinary excretion of beta2m were studied in 24 cadmium exposed workers with normal serum creatinine levels (less than 10 mg/l)) and no obvious tubular dysfunction. With increasing blood levels of cadmium beta2m was found to increase in serum. There was no concomitant increase in the urinary excretion of beta2m. Serum beta2m was not dependent on serum creatinine within the range studied. The results suggest that for evaluating renal glomerular function in cadmium exposed workers, it might be better to use the serum creatinine level, creatinine clearance or inulin clearance since beta2m might give some false positive results.     

Phosphate excretion during 24 h of hypoxia in conscious rats

The objective of this study was to investigate renal phosphate excretion during 24 h of hypoxia in conscious rats fed by total parenteral nutrition. Wistar rats weighing 190 g were exposed to hypoxia (inspired oxygen fraction = 0.10) or normoxia (inspired oxygen fraction = 0.21) for 24 h in a normobaric chamber. Renal clearance and hormonal studies were performed. The results showed a greater fractional excretion of phosphate (5.37 pL 0.07%, P < 0.05) and hypophosphataemia (7.40 pL 0.12 mg dL^-1, P < 0.01) in hypoxic rats (n = 10) than in normoxic rats (n = 13; 3.50 pL 0.37% and 8.02 pL 0.16 mg dL^-1, respectively). In addition, during hypoxia there was a significant decrease in the excretion of urinary adenosine 3′,5′-cyclic monophosphate per glomerular filtrate (2.97 pL 1.27 nmol dL^-1, P < 0.005), a parameter of the renal action of parathyroid hormone, and a stable level of serum parathyroid hormone (10.2 pL 2.6 ng mL^-1) (cf. normoxia: 8.57 pL 0.70 nmol dL^-1 and 8.0 pL 1.7 ng mL^-1, respectively). However, creatinine clearance and the renal adenosine triphosphate level, both of which affect adenosine 3′,5′-cyclic monophosphate excretion, were not different between the two groups. These data suggest that exposure of conscious rats to 24 h of hypoxia causes renal hyporesponsiveness to physiological levels of parathyroid hormone, which is manifested as a decrease in adenosine 3′,5′-cyclic monophosphate excretion. Phosphaturia is not a direct net effect of hypoxia and secondary hypocapnia on renal phosphate transport, which is known to be regulated by parathyroid hormone through adenosine 3′,5′-cyclic monophosphate.     

Tissue contents and urinary excretion of taurine after administration of L-cysteine and L-2-oxothiazolidine-4-carboxylate to rats

Tissue contents and urinary excretion of taurine were studied in rats after the administration of L-cysteine and its derivatives. Average taurine content in the liver of rats fed a 25% casein diet for 7 days increased 2-fold 2h after the intraperitoneal administration of 5 mmol of L-cysteine per kg of body weight, whereas that in rats fed a 5% casein diet for 2 days increased only slightly. The difference in the liver taurine contents between these two groups was discussed in relation to cysteine dioxygenase. Taurine contents in the heart, brain and blood did not differ significantly between these two groups or between the control and the group of rats which received L-cysteine. The increase in liver taurine concentrations after L-cysteine administration was much higher than that after L-cystine administration, suggesting a difference in their absorption. The intraperitoneal administration of 5 mmol/kg of L-2-oxothiazolidine-4-carboxylate (OTCA) resulted in a 3-fold increase in liver taurine content. The average increase in taurine excretion in the 24-h urine after OTCA administration corresponded to about 6.0% and that in the next 24-h urine to about 2.6% of OTCA administered, suggesting that nearly 10% of OTCA was metabolized to taurine and excreted in the urine.     

Renal effects of furosemide in glycerol induced acute renal failure of the rat

Summary The renal effects of furosemide in acute renal failure of the rat were studied using clearance and micropuncture techniques. Acute renal failure was induced by an intramuscular injection of 50% glycerol (10 ml/kg). Functional impairement of the glycerol treated animals consisted of a decrease in urinary sodium excretion, renal blood flow, total kidney GFR and effective filtration pressure of superficial nephrons. Effective filtration pressure was calculated from proximal free flow and stop flow pressure measurements.In contrast to control animals furosemide did not increase urine volume during acute renal failure due to a marked fall in GFR. Renal blood flow, as measured by an electromagnetic flowmeter, also decreased after furosemide in glycerol treated rats and increased in control animals. Furosemide reduced effective filtration pressure during acute renal failure to almost zero, whereas in control animals effective filtration pressure virtually remained constant.Supported by Deutsche Forschungsgemeinschaft.     

Increased urinary kallikrein excretion during prostaglandin E1 infusion in anaesthetized dogs and its relation to natriuresis and diuresis.

. The effect of intra-arterial prostaglandin E1 (PGE1) infusion on urinary kallikrein, sodium, potassium and water excretion was studied in normal anaesthetized dogs. 2. Infusion of PGE1 caused a dose-related increase in urinary excretion of kallikrein, sodium, potassium and water as well as an increase in renal blood flow (R.B.F.) and a fall in urinary osmolality and renal vascular resistance. 3. The changes occurred in the absence of appreciable changes in inulin clearance (Cin), arterial blood pressure, haematocrit, and plasma sodium and potassium concentrations. 4. The increased urinary kallikrein excretion correlated positively with the natriuresis, diuresis and kaliuresis and the increase in renal blood flow, but negatively with the urinary osmolality and renal vascular resistance. 5. It is concluded that renal kallikrein is involved in the renal response to arterial infusion of PGE1.     

Effect of Ethacrynic Acid on Plasma Renin Activity during Supine Exercise in Normal Subjects

Plasma renin activity, clearances of inulin (cin) and para-aminohippuric acid (cpah) , free water clearance (ch₂o) and urinary excretion of sodium and potassium were measured in 6 normal subjects at rest and during exercise in the supine position on a bicycle ergometer. The mean work load was 667 kpm/min and the duration of exercise 45 min. Ethacrynic acid, 50 mg, was injected i.v. at the start of exercise. Ethacrynic acid did not influence the normally occurring decrease in Cpah and C_in during exercise but abolished the renal concentration mechanism, indicating an inhibition of sodium reabsorption in the ascending loop of Henle. The urinary sodium cxcrction increased markedly, indicating an increased load of sodium in distal tubules. This was coincident with increased plasma renin activity. The findings indicate that changes in plasma sodium concentration or sodium load in the distal tubules are of minor importance for the increase in plasma renin activity during exercise.     

Urinary excretion of electrolytes during prolonged physical activity in normal man

Summary Nine normal young male students were studied during 2 days of relative rest, during 2 days of physical training and again during the succeeding 2 days of relative rest.Twenty-four hour urine collections showed that sodium and potassium excretion were lower during the exercise days, while urinary aldosterone excretion was increased. No differences in the 24-h urinary excretion of creatinine, calcium, and magnesium were found between the resting and exercise days.Hemoglobin concentration, hematocrit and red cell counts were decreased at 14 h and 42 h after exercise; these findings together with the increased serum bilirubin concentration could result from hemolysis.Plasma renin activity, angiotensin II and aldosterone concentration were increased 14 h after exercise but returned to baseline 42 h after exercise.Our data shows that one should take into account previous exercise when interpreting results of certain of these tests.     

Alkaline phosphatase isozymes of serum and urine and urinary protein in young men before and after running 3 km

Urine samples were collected from seven healthy male students 1 h before (control fraction) and 5–15 min (5–15 min fraction), 1 h (1-h fraction) and 3 h (3-h fraction) after running 3 km at a perceived exertion equal to approximately 15–17 Borg's scale. Venous blood was also collected from the subjects 1 h before and 1 h after the run. Urine was studied by measuring protein excretion, patterns of sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) of proteins, total alkaline phosphatase (ALP) excretion, intestinal alkaline phosphatase (IAP) excretion and ALP isozyme analysis by PAGE. Serum ALP was studied by measuring the total ALP activity and isozyme analysis by PAGE. The following results were observed: firstly, an increase was seen in the excretion of total protein, total ALP and IAP after the exercise. Statistical significance was seen in the first two of these parameters; secondly, albumin was the only detectable protein band in the control, 5–15 min and 3-h fraction by SDS-PAGE; thirdly, no significant changes were seen in total ALP activity and ALP isozymes in the serum; and fourthly, three to five ALP bands (bands 1, 2, 3, 4 and 5, from the cathodal side) were detected in the zymograms of urinary ALP. Bands 1–3 were high molecular mass ALP. Bands 4 and 5 were intestine-like and liver-like ALP, respectively. An increase of ALP activity of high molecular mass ALP and/or decrease of that of band 5 or appearance of band 4 were seen in the 1-h fraction, in comparision to the control fraction. We postulate that high molecular mass ALP were formed in the kidney by a combination of band 5 ALP and substance(s) induced by exercise. It is suggested from these results that urinary ALP isozymes are important elements in the investigation of the effects of exercise.     

阿托伐他汀对碘普罗胺引起的糖尿病大鼠肾小管上皮细胞凋亡的影响

 目的：观察糖尿病大鼠造影剂急性肾损伤(CI-AKI)发病过程中肾小管上皮细胞凋亡变化,并探讨阿托伐他汀对碘普罗胺引起的糖尿病大鼠肾小管上皮细胞凋亡的影响。方法：腹腔单剂量注射链脲佐菌素(STZ)建立糖尿病大鼠模型,饲养8周后糖尿病大鼠随机分为6组：空白对照组(N组)、糖尿病对照组(DM组)、糖尿病+造影剂组(DM+CM组)、糖尿病+造影剂+5 mg·kg-1·d-1阿托伐他汀组(ATO1组)、糖尿病+造影剂+10 mg·kg-1·d-1阿托伐他汀组(ATO2组)和糖尿病+造影剂+30 mg·kg-1·d-1阿托伐他汀组(ATO3组)。注入碘普罗胺注射液24 h后收集尿标本,检测尿肌酐(UCr)以及24 h尿微量白蛋白(24 h-UAlb),记录24 h尿量并计算尿微量白蛋白排泄率(24 h-UAER)。注射碘普罗胺后48 h收集血标本,检测血清肌酐(SCr)和血尿素氮(BUN),并计算内生肌酐清除率(CCr)。处死大鼠,摘取肾脏左肾行组织病理学分析,TUNEL检测凋亡情况及免疫组织化学法检测肾髓质Bax和Bcl-2蛋白的表达,并留取右肾,采用免疫印迹技术法检测肾髓质的Bcl-2及Bax蛋白表达情况。结果：与N和DM组比较,DM+CM组注入造影剂后SCr、BUN和24 h-UAER水平明显升高(P＜0.05),Ccr水平明显下降,肾小管上皮细胞的凋亡明显增加,肾髓质Bax蛋白表达升高,Bcl-2蛋白表达下降;与DM+CM组比较,ATO1、ATO2和ATO3组注入造影剂后SCr、BUN和24 h-UAER水平均有下降,CCr升高,肾小管上皮细胞的凋亡明显减少,肾髓质Bax蛋白表达下降,Bcl-2蛋白表达升高,且ATO3组的变化更为明显。结论: 碘普罗胺可诱导糖尿病大鼠肾小管上皮细胞的凋亡;阿托伐他汀能改善碘普罗胺引起的糖尿病大鼠肾功能损伤,此保护作用可能与之抑制碘普罗胺诱导的肾小管上皮细胞凋亡有关,且这种保护作用有剂量依赖性。