Study On The Protective Effect Of Unfractionated Heparin In A Rat Model Of Histone-induced Renal Microcirculation Dysfunction

Objective: To investigate the effect of intravenous injection of histone on the microcirculation of the cortical surface of the kidney and the protective effect of unfractionated heparin.Method: In this study,the adverse effects of increased extracellular histone on the body were studied by intravenous injection of histone.18 male Wistar rats(250±50g)were randomly divided into the control group,the histone group and the histone with heparin treatment group.After weighing,the rats were intraperitoneally injected with Nembutal,and then fixed on the heated surgical board.The rats were treated with tracheotomy and maintained autonomic ventilation(inhalation of air).The left femoral artery catheter(for monitoring rat heart rate and mean arterial pressure)and femoral vein catheterization(for intravenous administration).The rats were followed by a median incision in the abdomen and the microcirculation of the left renal cortical surface of the rat was observed.The histone group model was established by a one-time intravenous injection of 30mg/kg histone slowly.Histone with heparin treatment group was injected with 100IU/kg/h unfractionated heparin(dissolved in saline)intravenously after injection of histone.Rats were injected with histones(or saline)at 0 hour time point,and the heart rate and mean arterial pressure were observed for 6 hours.Using the incident dark field(IDF)micro video equipment to observe and record the changes of left renal cortex microcirculation of rats every two hours,and to measure the total small vessel density(TVD),the perfused small vessel density(PVD),the proportion of perfused vascular small vessels(PPV).Results: 1.After intravenous injection of histone,the heart rate and mean arterial pressure of the rats were not significantly changed in the experimental process.2.After intravenous injection of histone,the microcirculation of the renal cortical surface of the rat was changed,and the blood flow was slow and the microvasculature which could be observed was reduced.3.In histone group,the TVD was decreased(P<0.05),and PVD and PPV were significantly lower than those in the control group at 2 hour time point and after that(P<0.05).4.At the time of 2,4 and 6 hour time point,the microcirculation of histone heparin treatment group was better than that of histone group,and the area with no erythrocyte flow in microcirculation showed a decrease compared with that in histone group.The results of software analysis showed that TVD was higher than histone group at the 2,4,6 hour time point(P<0.05),but the improvement of PVD and PPV was not obvious(P>0.05).Conclusion: Intravenous injection of histone leads to microcirculation disturbance in the renal cortex of rats,and unfractionated heparin can improve the TVD of renal cortical surface microcirculation in histone induced rats.