Protection of erythropoietin on experimental spinal cord injury by reducing the expression of thrombospondin-1 and transforming growth factor-beta / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Erythropoietin (EPO) functions as a tissue-protective cytokine in addition to its crucial hormonal role in red cell production and neuron protection. This study aimed to determine the neuron protective effect of erythropoietin on experimental rats enduring spinal cord injury (SCI) by assessing thrombospondin-1 (TSP-1) level and transforming growth factor-beta (TGF-beta) in the development of a rat model of SCI.</p><p><b>METHODS</b>Sixty Sprague-Dawley rats were randomly assigned to three groups: sham operation control group, SCI group and EPO treatment group. By using a weight-drop contusion SCI model, the rats in the SCI group and EPO treatment group were sacrificed at 24 hours and 7 days subsequently. The Basso, Beattie, and Bresnahan (BBB) scores were examined for locomotor function. Pathological changes were observed after HE staining. The expressions of thrombospondin-2 (TSP-1) and TGF-beta were determined by immunohistochemical staining and Western blotting.</p><p><b>RESULTS</b>Slighter locomotor dysfunction was discovered and it was recovered abruptly as higher BBB scores were found in the EPO treatment group than in the SCI group (P < 0.01). Pathologically, progressive disruption of the dorsal white matter and regeneration of a few neurons were also observed in SCI rats. TSP-1 and TGF-beta expression increased at 24 hours and 7 days after SCI in the injured segment, and it was higher in the SCI group than in the EPO treatment group. Spinal cord samples from the animals demonstrated a TSP-1 optical density of 112.2 +/- 6.8 and TSP-1 positive cells of 5.7 +/- 1.3 respectively. After injury, the TSP-1 optical density and cell number increased to 287.2 +/- 14.3/mm(2) and 23.2 +/- 2.6/mm(2) at 24 hours and to 232.1 +/- 13.2/mm(2) and 15.2 +/- 2.3/mm(2) at 7 days respectively. When EPO treated rats compared with the SCI rats, the TSP-1 optical density and cell number decreased to 213.1 +/- 11.6/mm(2) and 11.9 +/- 1.6/mm(2) at 24 hours and to 189.9 +/- 10.5/mm(2) and 9.3 +/- 1.5/mm(2) at 7 days, respectively (P < 0.01). In the SCI rats, the TGF-beta optical density and positive neuron number were 291.4 +/- 15.2/mm(2) and 28.8 +/- 4.9/mm(2) at 24 hours and 259.1 +/- 12.3/mm(2) and 23.9 +/- 4.1/mm(2) at 7 days respectively. They decreased in the EPO treated rats to 222.8 +/- 11.9/mm(2) and 13.7 +/- 2.1/mm(2) at 24 hours and to 196.5 +/- 9.7/mm(2) and 8.7 +/- 2.2/mm(2) at 7 days (P < 0.01).</p><p><b>CONCLUSIONS</b>Increased expression of TSP-1 and TGF-beta can be found in the injured segment of the spinal cord at 24 hours and 7 days after injury. EPO treatment can effectively prevent pathological alterations from severe spinal cord injury by reduced expression of TSP-1 and TGF-beta.</p>

Changes in expression of adrenomedullin in the myocardium of streptozotocin-induced diabetic rats / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Adrenomedullin is a potent vasodilating peptide and involved in many cardiovascular diseases. However, whether adrenomedullin is involved in the pathogenesis of diabetic cardiomyopathy is still unknown. Our aim was to characterize the expression pattern of adrenomedullin in the myocardium of streptozotocin-induced diabetic rats.</p><p><b>METHODS</b>The weight, blood glucose, and urine glucose of 20 streptozotocin-induced diabetic rats were measured before and after model induction in the diabetic and control groups. The alteration of the adrenomedullin expression was explored in the left ventricular myocardium in both groups by immunohistochemistry. Changes in heart ultrastructure were also analyzed by using hemotoxylin and eosin staining and transmission electron microscopy. All data were analyzed by the independent samples t test.</p><p><b>RESULTS</b>The data of weight, blood glucose, and urine glucose had no significant difference between the control and the diabetic groups before animal model induction. Four weeks after the induction of diabetes, the differences between the two groups in weight, blood glucose, and urine glucose were distinct. When compared with the control group, the diabetic group showed ultrastructural changes including hypertrophy, fibrosis, myofibrillar disarrangements, mitochondrial disruption, and increase in nuclear membrane invaginations. A significant decrease of adrenomedullin expression was also observed in cardiac myocytes of the diabetic rats (P < 0.01).</p><p><b>CONCLUSIONS</b>Our study provides experimental evidence that hyperglycemia could damage cardiac myocytes. Down-regulation of cardioprotective peptide adrenomedullin in the myocardium of streptozotocin-induced diabetic rats may contribute to the diabetic cardiomyopathy and left ventricular dysfunction.</p>

Enhancement effect of caffeine on chemotherapy of osteosarcoma in Fischer 344/N rats / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To determine the enhancement effects of caffeine on chemotherapy of transplanted osteosarcoma in Fischer 344/N rats.</p><p><b>METHODS</b>Osteosarcoma-bearing Fischer 344/N rats were treated with cisplatin 2.5 mg/kg (Group DDP), caffeine 90 mg/kg x 2 d (Group caffeine), and cisplatin 2.5 mg/kg plus caffeine 90 mg/kg x 2 d (Group DDP+caffeine), and the control group was treated with normal saline in the same volume. All drugs were given by intra-peritoneum injection with micro-pump, in the rate of 0.5 ml/h. The tumor volume was measured and evaluated. The tumors were stained in TUNEL, and PCNA was detected with immunohistochemistry. The tumor growth inhibition rate, PCNA index and apoptosis index were calculated, and the survival time were recorded.</p><p><b>RESULTS</b>The tumor inhibition rate was -0.5219 +/-0.1429 in control group, 0.0362 +/-0.0957 in Group DDP, -0.4193 +/-0.1345 in Group caffeine, and 0.3646 +/-0.1313 in Group DDP+caffeine (P <0.01). PCNA index was 0.4587 +/-0.1312 in control group, 0.1847+/-0.0535 in Group DDP, 0.4381 +/-0.0706 in Group caffeine, and 0.0314 +/-0.0231 in Group DDP+caffeine (P <0.01). Apoptosis index was 0.0008 +/-0.0005 in control group, 0.0077 +/-0.0060 in Group DDP, 0.0011 +/-0.0003 in Group caffeine, and 0.0295 +/-0.0069 in Group DDP+caffeine (P <0.01). And the survival time was (33.63 +/-4.63)d in control group, (52.13 +/-11.74)d in Group DDP, (35.63 +/-5.15)d in Group caffeine, and (55.13 +/-16.23)d in Group DDP+caffeine (P <0.01).</p><p><b>CONCLUSION</b>Caffeine could enhance the anti-tumor effect of cisplatin in rat osteosarcoma.</p>