|Role of granulocyte colony-stimulating factor in paclitaxel-induced intestinal barrier breakdown and bacterial translocation in rats|
|Zhang Chi1; Xu Yang-guang2; Duan Xue-ning1; Liu Yin-hua1; Zhao Jian-xin1; Xu Ling1; Ye Jing-ming1|
|关键词||bacterial translocation paclitaxel granulocyte colony-stimulating factor|
|刊名||CHINESE MEDICAL JOURNAL|
|WOS标题词||Science & Technology|
|类目[WOS]||Medicine, General & Internal|
|研究领域[WOS]||General & Internal Medicine|
|关键词[WOS]||CELL-PROLIFERATION ; ACUTE-PANCREATITIS ; CROHNS-DISEASE ; PERMEABILITY ; INJURY ; TAXOL ; METHOTREXATE ; TRANSPORT ; THERAPY|
Background Chemotherapy causes breakdown of the intestinal barrier, which may lead to bacterial translocation. Paclitaxel, an anti-tubulin agent, has many side effects; however, its effect on the intestinal barrier is unknown. studies show that granulocyte colony-stimulating factor (G-CSF) plays an important role in modulating intestinal function, but these studies are not conclusive. Here, we investigated the effects of paclitaxel on the intestinal barrier, and whether G-CSF could prevent paclitaxel-induced bacterial translocation.
Methods Twenty-four male Sprague-Dawley rats were divided into three groups: control group, paclitaxel group and paclitaxel + G-CSF group. Intestinal permeability was measured by the urinary excretion rates of lactulose and mannitol administered by gavage. The mesenteric lymph nodes, spleen and liver were aseptically harvested for bacterial culture. Endotoxin levels and white blood cell (WBC) counts were measured and bacterial quantification performed using relative real-time PCR. Jejunum samples were also obtained for histological observation. Intestinal apoptosis was evaluated using a fragmented DNA assay and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate (dUTP)-biotin nick end-labeling staining. One-way analysis of variance and Fisher′s exact test were used to compare differences between groups.
Results Paclitaxel induced apoptosis in 12.5% of jejunum villus cells, which was reduced to 3.8% by G-CSF treatment. Apoptosis in the control group was 0.6%. Paclitaxel treatment also resulted in villus atrophy, increased intestinal permeability and a reduction in the WBC count. G-CSF treatment resulted in increased villus height and returned WBC counts to normal levels. No bacterial translocation was detected in the control group, whereas 6/8, 8/8, and 8/8 rats in the paclitaxel group were culture-positive in the liver, spleen and mesenteric lymph nodes, respectively. Bacterial translocation was partially inhibited by G-CSF.
Conclusions Paclitaxel disrupts the intestinal barrier, resulting in bacterial translocation. G-CSF treatment protects the intestinal barrier, prevents bacterial translocation, and attenuates paclitaxel-induced intestinal side-effects. Chin Med J 2011;124(12):1870-1875
|作者单位||1.Peking Univ, Hosp 1, Dept Gen Surg, Beijing 100034, Peoples R China|
2.Peking Univ, Sch Pharmaceut Sci, Dept Mol & Cellular Pharmacol, Beijing 100191, Peoples R China
|Zhang Chi,Xu Yang-guang,Duan Xue-ning,et al. Role of granulocyte colony-stimulating factor in paclitaxel-induced intestinal barrier breakdown and bacterial translocation in rats[J]. CHINESE MEDICAL JOURNAL,2011,124(12):1870-1875.|
|APA||Zhang Chi.,Xu Yang-guang.,Duan Xue-ning.,Liu Yin-hua.,Zhao Jian-xin.,...&Ye Jing-ming.(2011).Role of granulocyte colony-stimulating factor in paclitaxel-induced intestinal barrier breakdown and bacterial translocation in rats.CHINESE MEDICAL JOURNAL,124(12),1870-1875.|
|MLA||Zhang Chi,et al."Role of granulocyte colony-stimulating factor in paclitaxel-induced intestinal barrier breakdown and bacterial translocation in rats".CHINESE MEDICAL JOURNAL 124.12(2011):1870-1875.|