Low-dose Heparin For Early-intervention Of Sepsis Rats

Objective:To investigate the early-intervention effects of low-dose heparin on sepsis rats induced by CLP.Methods:96 female healthy Wistar rats were randomly divided into sham operation group (n=8), sepsis group (n=44) and heparin interfere group (n=44). Sepsis rats'models were prepared by cecal ligation and puncture (CLP). The sham operation group only flipped the cecum, and gave saline (30ml/(Kg.12h)) by subcutaneous injection; the sepsis group received saline (30ml/(Kg/12h)) by subcutaneous injection after CLP; the heparin interfere group received unfractionated heparin (UFH, 14U/(Kg.12h), total fluid is 30ml/12h) after CLP by subcutaneous injection. To observe and record the general state of the rats, after receiving the blood and lung tissue at different times, the rats were executed. The marks below were observed:â‘ The PT, APTT levels in plasma and the PLT counts in blood;â‘¡Detected MIF level by ELISA;â‘¢The pathological changes in lung tissues were observed with microscope after HE staining;â‘£The mortality was evaluated at 48h after CLP.Results:1) The rats of sepsis group and heparin group moved little after waked, crisp, piloerection, and appeared respiratory distress gradually. In abdominal cavity, the cecum became ischemia and necrosis, adhered with other intestinal canal. Erythroic fluid effused from some lung tissues when cutting off them.2) The platelets decreased at 6h after CLP; PT, APTT increased significantly at 24h after CLP. Using low-dose heparin immediately after finishing CLP could ameliorate the raise of APTT and the decrease of PLT (P=0.006,0.024). There was no significant difference between sepsis group and heparin interfere group in PT level (p=0.111). 3) The MIF level in sepsis rats'plasma was significantly elevated compared with the sham group, and the level of MIF was gradually increased within 48h. However, the MIF level reduced significantly when we used low-dose heparin (p<0.01), and the continuing use of heparin could maintain the MIF at a low level.4) In the sepsis group, the alveolar septum widened obviously compared with the sham group, and aggravated along with the developing of sepsis. There were lots of inflammatory cells in the interstitial lung tissue; some of them could be seen punctate hemorrhage and microthrombosis. The lung tissue injury lightened in the heparin intervention group comparing with the sepsis group; there was significant difference in the pathological score between sepsis group and heparin intervention group (P<0.01).5) The 48h-mortality was 65% in the sepsis group, while it was only 30% in the heparin interfere group (P<0.05).Conclusion:Low-dose heparin used early in the sepsis rats induced by CLP could ameliorate the disorder of blood coagulation, and markedly decrease the plasmic MIF level as well as lung injury, and could reduced 48h mortality.