Experimental study on cyclosporine A impairing the rat myocardial tissue
10.3760/cma.j.issn.1000-4955.2009.04.017
- VernacularTitle:环孢霉素A致大鼠心肌组织损伤的实验研究
- Author:
Jin-feng, YU
;
Yang, LI
;
Gai-gai, ZHANG
;
Yu, FU
;
Zhao-ying, ZHANG
;
Xin-hua, YIN
- Publication Type:Journal Article
- Keywords:
Cyclosporine A;
Myocardium;
Malondialdehyde;
Superoxide dismutase;
Apoptosis
- From:Chinese Journal of Endemiology
2009;28(4):413-416
- CountryChina
- Language:Chinese
-
Abstract:
Objective To observe the impairment of different doses of cyclosporine A (CsA) to the rat myocardial tissue to offer scientific evidence for the long-term safe application of CsA in heart transplantation. Methods Eighty-four female Wistar rats, each weighing of (200 ± 25)g, were randomly divided into 12 groups. On days 7,14,21 after a constant peritoneal injection of CsA(0,5,10,15 mg/kg) and 1 ml physiological saline in control group, the rats were put to death, the rat myocardial tissue taken, to observe the pathologic and structural changes of the tissue cells under light microscope and electron microscope. The contents of rat myocardium tissue malondialdehyde(MDA) and superoxide dismutase(SOD) were measured;cardiomyocyte apoptosis was detected and accounted, apoptosis index(AI) was measured with the method of TUNEL. Results Small dose of CsA(5 mg/kg)had no obvious effects on cardiac tissue, in CsA groups of 10 mg/kg and 15 mg/kg, under the light microscope, there appeared edema, degeneration and necrosis of myocardium, part of cardiac myocyte had different level cavity;under the electron microscope, there appeared mitochondria damage, nucleus shrinkage and chromatic margination, part of cardiac myocyte had focus cavity. There was dilated endoplasic reticulum in the sarcoplasm. The effects of different time and dose on MDA content of rat myocardium tissue had statistical significance (F = 6.37,10.15, both P < 0.05). Interaction between time and dose existed statistical significance (F=7.14, P< 0.05). The MDA contents of CsA group of 10 mg/kg and 15 mg/kg were [(2.29 ± 0.18), (3.10 ± 0.45), (2.57± 0.37)nmol/L] and [(3.09±0.63), (3.32 ±0.52), (3.34 ± 0.29)nmol/L] on days 7,14,21 after a constant peritoneal injection of CsA, which were obviously higher than the control group [(1.98 ± 0.20), (2.04 ± 0.52), (1.99 ± 0.26) nmol/L, all P < 0.05], respectively. The effects of different time and dose on SOD activity of rat myocardium tissue had statistical significance(F = 8.43,11.69, both P < 0.05). Interaction between time and dose existed statistical significance(F = 9.86, P < 0.05). The SOD activity of CsA groups of 10 mg/kg and 15 mg/kg were (15.95 ± 1.00), (12.74 ± 1.31), (14.01 ± 0.81)nmol/L and (13.04 ± 1.01), (14.68 ± 0.81), (14.01 ± 0.63)nmol/L on days 7,14,21 after a constant peritoneal injection of CsA, which were obviously higher than the control group [(10.38 ± 0.80), (9.73 ± 0.58), (10.20 ± 0.26)nmol/L, all P < 0.05], respectively. Apoptosis nucleus appeared huffy or brown under the light microscope. The effects of different time and dose on AI of rat myocardium tissue had statistical significance (F = 10.02,20.46, both P < 0.05). Interaction between time and dose existed statistical significance (F = 15.73,P < 0.05). The AI of CsA groups of 10 mg/kg and 15 mg/kg were (6.91 ± 0.70)%, (11.10 ± 2.05)%,(19.81 ± 5.00)% and (11.02 ±2.02)%,(15.51 ± 1.31)%,(33.40±6.60)% on days 7,14,21 after a constant peritoneal injection of CsA, which were obviously higher than the control group [(4.40 ± 0.13)%, (4.60± 1.20)%, (5.20 ± 1.10), all P < 0.05] and CsA group of 5 mg/kg [(4.60 ± 0.10)%, (5.00±2.11)%, (5.43± 1.11)%, all P < 0.05], respectively. Conclusion Small dose of CsA has no obvious effects on cardiac tissue, but large dosage can induce myocyte apoptosis and damage by causing oxidative stress;after implantation, attention should be paid to cardiac impairment due to constant large dosage of CsA.
