摘要:目的:探讨卡配因抑制剂3（MDL28170）对新生大鼠缺氧缺血性脑损伤(HIBD)神经细胞凋亡的影响。方法:建立新生SD大鼠HIBD模型,治疗组于缺养缺血后即刻、2 h、4 h腹腔内注射MDL28170,对照组及手术组同时予生理盐水。缺氧缺血后24 h用免疫组化方法观察大脑皮质及海马CA1区Caspase3 蛋白表达、TUNEL法检测细胞凋亡,观察组织病理改变并计算海马神经元死亡数,透射电镜观察细胞超微结构。结果:缺氧缺血后24 h缺血侧大脑皮质及海马CA1区Caspase3和TUNEL阳性细胞数较对照组明显增加,透射电镜证实有凋亡细胞;MDL28170可减少阳性细胞数量,抑制神经元死亡,差异有显著性(Plt;0.05)。结论:MDL28170可通过抑制神经凋亡而对新生大鼠HIBD具有一定保护作用。Abstract: Objective: To investigate the effect of (Calpain inhibitor3) MDL28170 on neural apoptosis in a neonatal model of hypoxicischemic brain damage (HIBD). Methods: A neonatal model of HIBD was established, 7dayold SD rats were divided into three groups. The treatment group received MDL28170(ip) at 0 h,2 h,4 h after HI, whereas the other two groups were administered normal saline simultaneously. The expression of caspase3 (by immunohistochemistry), neural apoptosis (by TUNEL) in cortex and hippocampus ipsilateral to the insult were observed 24 h after HI; hippocampal CA1 neural loss and electromicroscopic changes were assessed at the same time. Results: Apoptotic body was observed by electromicroscopy. Caspase3 positive cells and apoptotic cells increased significantly in the ipsilateral cortex and hippocampal CA1 region compared to the control, and MDL28170 reduced the number of positive cells, attenuated CA1 neural loss with significance (Plt;0.05). Conclusion: It is suggested that MDL28170 may protect the brain of neonatal rats after HIBD by suppressing neural apoptosis.
Objective To investigate the correlation between the plasma endothelin (ET) and gastric mucosal pathology.MethodsIn this experiment,seven dogs who experienced common bileduct ligation were in experiment group, the other three dogs who underwent shamoperation were control group. By using specific radio immunological method, the plasma ET levels were determined in dogs before and after 1,4,7 d. The total bilirubin levels were determined before and after 1,4,7 d after operation by using carbazotic acid method.The gastric mucosa,7 d after operation, was cut into slices and was examined under the electron microscope and the light microscope.Results In the experiment group,the levels of ET and total bilirubin rose continually and were higher than those in control group. Vascular congestion and oedema were seen in gastric mucosa of common bileduct ligated dogs. Under the electron microscope, we could see the dilated blood capillary and sludging of blood,the intenstitial mucusa cells oedema. Conclusion The increase of plasma ET might lead to impairment of mucosal microcirculation,which might be one of the pathogens that could induce the gastric mucosal damages in common bileduct ligated dogs.
ObjectiveTo evaluate the effect of polymorphonuclear neutrophils (PMN) on liver damage in acute pancreatitis. MethodsSeventytwo wistar rats were randomly divided into acute pancreatitis (AP) group, acute pancreatitis with PMN depleted (APD) group and sham operation (SO) group. Liver damage was assessed by histological changes and the level of alanine aminotransferase (ALT) in serum. The number of PMN infiltration in liver was reflected by myeloperoxidase (MPO). ResultsMPO significantly increased from 6 to 24 hours in AP and APD groups. However, the level of MPO was significantly higher in AP group than that in APD group. ALT significantly increased from 3 to 24 hours in these two groups, but the level of ALT was significantly lower in APD group than that in AP group. Meanwhile, the hepatic pathological changes were more severe in AP group than that in APD group. ConclusionPMN play an important role in liver damage during acute pancreatitis.
In order to observe activity of tumor necrosis factor (TNF) in the serum, pancreatic histopathological damage, as well as their relationships in acute necrotizing pancreatitis (ANP), thirty five SD rats were randomly divided into 7 groups according to their sampling time with 5 in each group. ANP was induced by retrograde infusion of 5% sodium taurocholate through biliopancreatic duct in 6 experimental groups (Group B1～B6).Blood and pancreatic tissue samples were obtained at hour 0,0.5,2,4,6 or 8 respectively when the animals were sacrificed.Results showed that serum level of TNF activity rose significantly in Group B2,and reached the maximal value in Group B4.The pancreatic histopathological damage in ANP rats was getting worse along with time. Serum TNF activity had close relation to pancreatic histopathological score (r=0.63, Ｐ＜0.01),suggesting that serum TNF may play an important role in the process of deterioration of pancreatic tissue damage during ANP.
The mumber of Polymorphonuclear leukocyte (PMN) in hepatic tissue increased in the rats with cholangitis, PMN infiltration was mainly in the hepatic sinus in the early stage; and PMN infiltration presented around the hepatocytes 12 hours after infection. Degeneration and necrosis of the hepatic cells was also observed in the rats with acute cholangitis. Only 40 percent of the rats survived 24 hours after infection. Depletion of circulating PMN decreased the damage and necrosis of hepatocytes and improving the survival rate of the infected rats. The results suggest that PMN infiltration plays an important role in hepatic damage in acute cholangitis.
The purpose of this study was to determine the contribution of endotoxin (ET) in ocurrence and progression of acute pancreatitis (AP). The results indicated that correlation of ET changes with multiple organ damage in AP. The degree of ET elevation correlated well with the severty of AP. The level of plasma ET of severe AP patients was much higher than that of mild AP patients (Ｐ＜0.05). The chance of multiple organ damage got greater while the plasma ET level got higher. Moreover, the severety change of severe AP correlated with the change of plasma ET level. In other words, the ET level was reduced while the disease was recovering, elevated while it was becoming worse and maintained high level in dead cases. We think that plasma ET level can be used as a reference for differenciating mild AP with severe AP and a predictor for the prognosis of AP.
The damage effects of the pure tumor necrosis factor (TNF) on the normal animals were observed. Eighteeen rabbits were divided into two groups, eight in tested group and ten in control group. 0.5mg per kg of the pure rabbit TNF was given to each animal of the tested group. Results:The symptoms similar to that induced by endotoxin appeared after the TNF injection. The functions of the main organs were markedly damaged. The arterial blood pressure of most animal was low. The weight ratio of the orgen to the body was raised. The pathologic changes were similar to those of the multiple organ failure (MOF) model. Most of the animal died before the end of the experiment. The results suggest that pure TNF could indece multiple organ damages similar to those of MOF.
Objective To elucidate the etiology of DNA impairment of type Ⅱ alveolar epithelial cells(AT-II) of the rats fed with low selenium and high cadmium fodder，and the effect of Vitamin C.Methods With single cell gel electrophoresis technique，we observed the joint action of selenium，cadmium and vitamin C on DNA damage in AT-II cells of the eight groups of rats fed separately with：normal （2 groups），high Cd，high Cd+high VC，low Se+high Cd，low Se+high Cd+high VC，high Se+high Cd and high Se+high Cd+high VC fodder for 14 weeks.Results Compared with the control，there was no DNA changes have been observed in the high Se+high Cd+high VC group.However，in the high Se+high Cd group and high Cd+high VC group，DNA damage of AT-II cells can be detected clearly；in the low Se+high Cd+high VC group and high Cd group，the degree of the DNA damage is more serious than the above two groups；in the low Se+high Cd group，the extent of the DNA damage was the most serious on all of the groups be studied.Conclusion It is suggested that Se deficiency and simultaneously Cd overabundance may damaged DNA of AT-II cells of the rats significantly，however，Vitamin C may protect AT-II against the injury effectively.
Objective To investigate the effects of vaporized perfluorocarbon( PFC) inhalation on histopathology of lung, small intestine, liver and kidney of acute lung-injured rabbits. Methods Eighteen New Zealand rabbits were randomly divided into 3 groups, ie. a conventional mechanical ventilation( CMV)group, a PFC group, and a control group. The rabbits were mechanical ventilated and intratracheally infused artificial seawater to induce acute lung injury. After ALI was established( PaO2 /FiO2 lt; 200 mm Hg) , the CMV group received CMV for 6 hours. The PFC group received PFC inhalation for 2 hours, and followed by CMV for 4 hours. And the control group was weaned from ventilation. Then they were sacrificed for histopathological measurement of lung, small intestine, liver and kidney. Results The rabbits in the control group died in 15 minutes after discontinuation of ventilation. Vaporized PFC inhalation can obviously improve oxygenation and attenuate the damage of the lung in contrast to CMV. Mild improvement was observed in small intestine, liver and kidney after vaporized PFC inhalation, but without statistical significance. Conclusion Vaporized PFC inhalation can improve oxygenation and attenuate lung injury in histopathology,but have no apparent protective effects on extra-pulmonary organs.
Objective To investigate the effects of ovarian tissue cryopreservation by needle immersed vitrification (NIV) method and subsequently orthotopic transplantation on ovarian function reconstruction in chemotherapy-induced ovary damage rat model. Methods A total of 52 matured virginal female Wistar rats at age of 8-9 weeks housed in specific-pathogen-free facilities, weighing 250-300 g. Vaginal smears were obtained daily, 50 rats having at least 2 consecutive normal estrous cycles were included in the experiment. Ten rats were selected as donors randomly, and NIV method was used for cryopreserving ovarian tissues. The remaining 40 rats were divided into 3 groups according to different treatments: cyclophosphamide group (C group, n=14), cyclophosphamide/transplantation group (C/T group, n=12), and control group (NS group, n=14). In C group and C/T group, the rats received peritoneal injection of cyclophosphamide every day for 21 days to establish the chemotherapy-induced ovary damage models; and then the frozen-thawed ovarian tissues orthotopically transplanted into the left ovarian bursae in C/ T group. The rats received peritoneal injections of 0.9% saline solution every day for 21 days in NS group. Estrous cycle recovery time, ovary weight, morphology change of ovarian tissues, and follicle count were compared among 3 groups. Results One rat died at 2 days after transplantation in C/T group; the other rats survived to the completion of the experiment. At 4 weeks after the end of injection, no significant difference in body weight was found among 3 groups (P gt; 0.05). The rats of NS group had regular estrous cycle, but cyclic changes in vaginal smears were observed in C group and C/T group during cyclophosphamide treatment. The median estrous cycle recovery was 9 days (95%CI: 7.9-10.1 days) in C group, and was 6 days (95%CI: 4.9-7.1 days) in C/ T group, showing significant difference (χ2=6.571, P=0.010). The ovarian weight showed an obvious downtrend in C group at 4 weeks after cyclophosphamide treatment, and an upward trend was observed in C/T group. The ovarian grafts survived and grew well in C/T group. Primordium follicles and primary follicles in C/T group and NS group were significantly more than those in C group (P lt; 0.05), but no significant difference was found between NS group and C/T group (P gt; 0.05). There was no significant difference in secondary follicles and antral follicles among the 3 groups (P gt; 0.05). Conclusion The method of ovarian tissue cryopreservation by NIV and subsequently orthotopic transplantation can significantly shorten the estrous cycle recovery time in chemotherapy-induced ovary damage rat model. Ovarian grafts grow well, follicle count is similar to normal level. So it has the potential ability of ovarian endocrine and fertility reconstruction after chemotherapy.