| Objective: To compare the nephrotoxic levels induced by HOCM and LOCM via animal experiments. To investigate the expression of caludin-1, caspase-3, Angâ…¡level in radiographic contrast nephropathy and study possibilities of protection of forsinopril sodium/telmisartan against radiographic contrast nephropathy and possible mechanisms.Methods: Forty eight healthy SD rats with an average weight of 200 grams were chosen as study objects. The rats were balanced in terms of gender. They were randomly divided into six groups: glycerol group, HOCM group, LOCM group, forsinopril group, telmisartan group and control group. The rats with normal range of urine protein were selected for experiments. All groups were prohibited from drinking for 24 hours. Then they were treated with intramuscular injection with 25ï¼…hypertonic glycerol saline(10ml/kg) except for the normal group. Normal drinking was resumed afterwards. Urine protein level was checked in the rats after 24 hours. Modeling of the rats was judged successful if relevant urine protein levels ranged from ++ to +++. Except for glycerol group and normal group, the rats were injected with iodine of the same concentration level(300mg/ml) and high osmolar contrast media of the same dose(diatrizoate meglumine) or low osmolar contrast media(Ominipaque) via vena caudali. Prevention group was treated with intragastric administration of forsinopril sodium(monopril: 10mg/kg), telmisartan(micardis tablet: 5mg/kg) one hour before vena caudali injection of high osmolar contrast media. Distilled water was freshly prepared before all used. Rats were killed 48 hours after injection of contrast media. Blood samples were taken from abdominal aorta in order to check serum creatinine, blood urea nitrogen and angiotensinâ…¡. Nephrotic homogenate was sampled and centrifuged. Then the nephrotic activation of caspase-3 in supernate was detected via chromatometry. Some other nephric tissues were formalin-fixed after a period of 12 to 24 hours, then dehydrated, embedded and sectioned. The expression of claudin-1 was detected by immunohistochemical methods and cell apoptosis of HKC was also detected by TUNEL.Results:1. An increase of Scr and BUN was observed in both HOCM group and LOCM group. A severer damage on nephric tubules was also observed compared with glycerol group. Massive apomorphosis of vacuole, albumen cast and tubular necrosis were also evidenced. HOCM could cause more obvious nephrotoxic effect than LOCM does with the same iodin hydronium concentration level. Obvious cell apoptosis could be observed in contrast media group. A higher apoptosis ratio could also be observed in HOCM group compared with LOCM group and prevention group. Statistic could prove all the compared results.2. The HKC cell expression of claudin-1 was increased when treated with contrast media. Compared with normal group, the expression of Caspase-3 is up-regulation in all groups, especially in HOCM group.3. Companied with less damage on nephric tubules, a lower level of Angâ…¡and a lower ratio of cell apoptosis, BUN and Scr levels dropped significantly in prevention group treated with forsinopril sodium and telmisartan tablet than in contrast media groups.Conclusions:1. Cell apoptosis could be induced by both HOCM and LOCM. However LOCM had less remarkable effects on cell apoptosis than HOCM does.2. Caspase-3, claudin-1 and Ang-â…¡could play a part in RCN.3. Forsinopril sodium and telmisartan could play a protection role in RCN and might inhibit both apoptosis and damage on nephric tubules by increasing of angiotensinâ…¡and caspase-3 active level induced by contrast media.4. The expression of Claudin 1 was strengthened when treated with Radiographic contrast media. |
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