Sublethally irradiated mice were immediately treated with 250 mg/kg Ligustrazine Phosphiatis intraperitoneally twice a day for seven days, and the bone marrow sections of ulna were observed. On the 5th day, the number...Sublethally irradiated mice were immediately treated with 250 mg/kg Ligustrazine Phosphiatis intraperitoneally twice a day for seven days, and the bone marrow sections of ulna were observed. On the 5th day, the number of bone marrow microvessels of the Ligustrazine group was much greater than that of the control group. On the 7th day, the amount of the control group decreased to normal, while the ligustrazine group was still increasing, and the microvessel area was enlarged obviously. The percentage of the hematopoietic tissue volume in bone marrow between the two groups had no significant difference in the first 7days. On the 7th day after irradiation, the peripheral neutrophilic granulocytes increased in the Ligustrazine group- The results suggested that early use of Ligustrazine after acute radiation injury might improve the blood supply of bone marrow, and be helpful for recovery of hematopoiesis.展开更多
After irradiated by & Gy 60Co γ-ray, mice were intraperitoneally injected immediately with 0.2 ml 100 % compound blood-activating soup twice a day for 10 days. The in situ ulnar bone marrow partial pressure of ox...After irradiated by & Gy 60Co γ-ray, mice were intraperitoneally injected immediately with 0.2 ml 100 % compound blood-activating soup twice a day for 10 days. The in situ ulnar bone marrow partial pressure of oxygen (PbO2) was determined in vivo before, during and after irradiation respectively. The bone marrow sections in the same part were observed. Our results showed that the normal murine ulnar PbO2 was 12.72±1. 05kpa. During irradiation, the level of PbO2 decreased to 10. 78±1. 17 kpa (P＜0. 001). And 3 days after irradiation, PbO2 decreased to 9. 75±0. 52 kpa, suggesting that the commonly used 'blood-activating and stasis-eliminating' Chinese drugs could promote the rehabilitation and proliferation of bone marrow microvessels in the acute radiation injured mice, expand their areas, increase the oxygen supply of bone marrow microenviroment, thereby leading to PbO2 much higher increase than that of control group. It is also helpful in the proliferation and rehabilitation of hematopoietic cells.展开更多
Objective: To study the expressions of basic fibroblast growth factor (bFGF) and its receptor (bFGFR) in bone marrow of mice with acute radiation injury, and to evaluate the effect of Ligustrazine (Lt) on them. Method...Objective: To study the expressions of basic fibroblast growth factor (bFGF) and its receptor (bFGFR) in bone marrow of mice with acute radiation injury, and to evaluate the effect of Ligustrazine (Lt) on them. Methods: Fifty-six Kunming mice of clean grade were randomly divided into 3 groups, the normal group, the control group and the Lt group. Mice in the latter two groups were once homogeneously systemic irradiated with 6.0 Gy of 60 Co, with the absorption dose rate of 0. 56 Gy/min, then treated with saline (0.2 ml/ mice) or Lt (2 mg/mice) respectively, twice a day through gastrogavage for successive 13 days. Mice were sacrificed in batch on the 3rd, 7th and 14th day by cervical dislocation to collect the bilateral femoral bone marrow for preparing bone marrow mono-nuclear cell (BMMNC) suspension. The bFGFR expression on surface of BMMNC was determined by flow cytometry; and the bFGF expres-sion level in one side of femoral bone marrow tissue was detected by immunohistochemistry with SABC-AP assay. Results: The bFGF expression in bone marrow of mice on the 3rd, 7th and 14th day after acute radiation injury all were significantly lower than that of the normal mice (P<0.05 or P<0.01). The expressions of bFGF and bFGFR in the Lt group detected were significantly higher than that in the control group detected at the corresponding time points (P<0.05 or P < 0.01). Conclusion:By way of enhancing bFGF expression in bone marrow and bFGFR expression on surface of BMMNC to accelerate the repairing of hemopoietic micro-environment in bone marrow might be one of the mechanisms of Lt in promoting hemopoietic function reconstitution after acute radiation injury.Original article on CJITWM (Chin) 2004;24(5):439展开更多
Six patients treated with human leukocyte antigen (HLA)-mismatched bone marrow transplantation (BMT) suffered from grade I to IV acute graft-versus-host disease (aGvHD) after engrafting. Up to date, 4 patients with gr...Six patients treated with human leukocyte antigen (HLA)-mismatched bone marrow transplantation (BMT) suffered from grade I to IV acute graft-versus-host disease (aGvHD) after engrafting. Up to date, 4 patients with grade I to II GvHD have lived for over 2920, 910, 740 and 680 days, respectively. Two other patients died of grade IV hyperacute GvHD. The results seem to indicate that patients in mismatched BMT have a high incidence of aGvHD within a month. The severity of aGvHD is positively correlated with the degree of HLA mismatching. The higher the degree of mismatch of HLA, the earlier and the more severe the aGvHD occurrs. The cutaneous lesion of the patient with GvHD is severe and of ten complicated by mucositis. Lethal hyperacute GvHD must be considered when a patient shows following signs at beginning: (1) The symptoms appear early (within 2weeks) ;(2) peripheral white blood cell count does not recover (<0. 5×109/L) to normal; and (3) high fever persists. In the epidermal ultrastructure of patients, besides acantholysis, autophagic degeneration of keratinocytes,and satellite cell dyskeratosis, there were scattered necrotic keratinocytes, breaking and thickening of basal membrane and presence of a lot of pigment in the intercellular space. These imply that the ultrastructural damages in the skin of patients with aGvHD after mismatched transplantation are more severe than after matched ones.展开更多
Hematopoietic syndrome of acute radiation syndrome(h-ARS)is an acute illness resulted from the damage of bone marrow(BM)microenvironment after exposure to radiation.Currently,the clinical management of h-ARS is limite...Hematopoietic syndrome of acute radiation syndrome(h-ARS)is an acute illness resulted from the damage of bone marrow(BM)microenvironment after exposure to radiation.Currently,the clinical management of h-ARS is limited to medication-assisted treatment,while there is still no specific therapy for the hematopoietic injury from high-dose radiation exposure.Our study aimed to assemble biomimetic three-dimensional(3D)BM microniches by co-culture of hematopoietic stem and progenitor cells(HSPCs)and mesenchymal stem cells(MSCs)in porous,injectable and viscoelastic microscaffolds in vitro.The biodegradable BM microniches were then transplanted in vivo into the BM cavity for the treatment of h-ARS.We demonstrated that the maintenance of HSPCs was prolonged by co-culture with MSCs in the porous 3D microscaffolds with 84μm in pore diameter and 11.2 kPa in Young’s modulus compared with 2D co-culture system.Besides,the minimal effective dose and therapeutic effects of the BM microniches were investigated on a murine model of h-ARS,which showed that the intramedullary cavity-injected BM microniches could adequately promote hematopoietic reconstitution and mitigate death from acute lethal radiation with a dose as low as 1000 HSPCs.Furthermore,the mRNA expression of Notch1 and its downstream target gene Hes1 of HSPCs were increased when co-cultured with MSCs,while the Jagged1 expression of the co-cultured MSCs was upregulated,indicating the significance of Notch signaling pathway in maintenance of HSPCs.Collectively,our findings provide evidence that biomimetic and injectable 3D BM microniches could maintain HSPCs,promote hematopoiesis regeneration and alleviate post-radiation injury,which provides a promising approach to renovate conventional HSPCs transplantation for clinical treatment of blood and immune disorders.展开更多
Objective: To observe the effect of Chinese herbal medicine in alleviating acute toxic adverse effect of radiotherapy and on growth of stromal cells in bone marrow. Methods: Seventy two patients with nasopharyng...Objective: To observe the effect of Chinese herbal medicine in alleviating acute toxic adverse effect of radiotherapy and on growth of stromal cells in bone marrow. Methods: Seventy two patients with nasopharyngeal carcinoma (NPC) were randomly divided into two groups. Radical radiotherapy was applied to both groups. In the radiotherapeutic period, to the 36 patients in the treated group, Yiqi Huoxue Yangyin Recipe (YHYR) was given additionally by oral taking and compressing on radiation area, and to the 36 patients in the control group, vitamin B 12 solution was given for gargling or compressing. Experimental study was carried out in rats of two groups, irradiated with 5.0 Gy X ray and treated with YHYR or normal saline intraperitoneally, to observe the colony forming unit fibroblastoid (CFU F) in cultured bone marrow stromal cells (BMSC), taken from the rats at different time.Results: The oral mucomembranous radiation damage occurred in 47.2% of the treated group when the dose of radiation reached to 41.4±9.4 Gy, while in the control group, it was 91.7% when the dose reached to 30.9±8.9 Gy. The skin radiation damage occurrence rate in the two groups was 13.9% and 33.3% respectively when the dose of radiation reached to 50.2±5.6 Gy and 43.2±6.3 Gy respectively. Comparison of the two groups showed significant difference ( P <0.01), the radiation damage was significantly slighter in the treated group. Experimental study showed that the rats in the two groups were significantly different in occurrence and degree of bone marrow function inhibition, P <0.01. The numbers of CFU F in cultured BMSC of radiation damaged rats taken at respective different culture time were also significantly different between the two groups, P < 0.01 .Conclusion: YHYR could significantly reduce acute radiation damage of mucomembrane and skin, alleviate the inhibition on bone marrow function, and eliminate the injury of radiation on BMSC.展开更多
目的:建立一个稳定可靠的异基因骨髓移植(allogeneic bone marrow transplantation,Allo-BMT)急性移植物抗宿主病(acute graft-versus-host disease,aGVHD)动物模型,为Allo-BMT中aGVHD研究提供理想的实验平台。方法:以雄性C57BL/6(H-2b...目的:建立一个稳定可靠的异基因骨髓移植(allogeneic bone marrow transplantation,Allo-BMT)急性移植物抗宿主病(acute graft-versus-host disease,aGVHD)动物模型,为Allo-BMT中aGVHD研究提供理想的实验平台。方法:以雄性C57BL/6(H-2b)为供鼠,雌性BALB/C(H-2d)为受鼠,受鼠致死性全身照射(total body irradiation,TBI)(8.0Gy)预处理后,在移植物中混合不同比例的供鼠骨髓细胞和脾细胞以引起不同程度的aGVHD。根据存活期、外周血白细胞计数、临床表现及病理检查等判断aGVHD程度。结果:单纯异基因骨髓组只有部分小鼠出现aGVHD,75%的小鼠长期存活(>30d)。混合不同比例的供鼠骨髓细胞和脾细胞的Allo-BMT小鼠出现aGVHD的时间和程度均有差异,其中骨髓与脾细胞1.5:1或1:1混合组小鼠,均可在相对集中的时间内(8～15d)观察到典型的aGVHD临床和病理改变。结论:建立Allo-BMT aGVHD模型需要加入一定比例的脾细胞,供鼠骨髓与脾细胞1.5:1或1:1混合进行的Allo-BMT,可作为理想的aGVHD动物模型。展开更多
文摘Sublethally irradiated mice were immediately treated with 250 mg/kg Ligustrazine Phosphiatis intraperitoneally twice a day for seven days, and the bone marrow sections of ulna were observed. On the 5th day, the number of bone marrow microvessels of the Ligustrazine group was much greater than that of the control group. On the 7th day, the amount of the control group decreased to normal, while the ligustrazine group was still increasing, and the microvessel area was enlarged obviously. The percentage of the hematopoietic tissue volume in bone marrow between the two groups had no significant difference in the first 7days. On the 7th day after irradiation, the peripheral neutrophilic granulocytes increased in the Ligustrazine group- The results suggested that early use of Ligustrazine after acute radiation injury might improve the blood supply of bone marrow, and be helpful for recovery of hematopoiesis.
文摘After irradiated by & Gy 60Co γ-ray, mice were intraperitoneally injected immediately with 0.2 ml 100 % compound blood-activating soup twice a day for 10 days. The in situ ulnar bone marrow partial pressure of oxygen (PbO2) was determined in vivo before, during and after irradiation respectively. The bone marrow sections in the same part were observed. Our results showed that the normal murine ulnar PbO2 was 12.72±1. 05kpa. During irradiation, the level of PbO2 decreased to 10. 78±1. 17 kpa (P＜0. 001). And 3 days after irradiation, PbO2 decreased to 9. 75±0. 52 kpa, suggesting that the commonly used 'blood-activating and stasis-eliminating' Chinese drugs could promote the rehabilitation and proliferation of bone marrow microvessels in the acute radiation injured mice, expand their areas, increase the oxygen supply of bone marrow microenviroment, thereby leading to PbO2 much higher increase than that of control group. It is also helpful in the proliferation and rehabilitation of hematopoietic cells.
文摘Objective: To study the expressions of basic fibroblast growth factor (bFGF) and its receptor (bFGFR) in bone marrow of mice with acute radiation injury, and to evaluate the effect of Ligustrazine (Lt) on them. Methods: Fifty-six Kunming mice of clean grade were randomly divided into 3 groups, the normal group, the control group and the Lt group. Mice in the latter two groups were once homogeneously systemic irradiated with 6.0 Gy of 60 Co, with the absorption dose rate of 0. 56 Gy/min, then treated with saline (0.2 ml/ mice) or Lt (2 mg/mice) respectively, twice a day through gastrogavage for successive 13 days. Mice were sacrificed in batch on the 3rd, 7th and 14th day by cervical dislocation to collect the bilateral femoral bone marrow for preparing bone marrow mono-nuclear cell (BMMNC) suspension. The bFGFR expression on surface of BMMNC was determined by flow cytometry; and the bFGF expres-sion level in one side of femoral bone marrow tissue was detected by immunohistochemistry with SABC-AP assay. Results: The bFGF expression in bone marrow of mice on the 3rd, 7th and 14th day after acute radiation injury all were significantly lower than that of the normal mice (P<0.05 or P<0.01). The expressions of bFGF and bFGFR in the Lt group detected were significantly higher than that in the control group detected at the corresponding time points (P<0.05 or P < 0.01). Conclusion:By way of enhancing bFGF expression in bone marrow and bFGFR expression on surface of BMMNC to accelerate the repairing of hemopoietic micro-environment in bone marrow might be one of the mechanisms of Lt in promoting hemopoietic function reconstitution after acute radiation injury.Original article on CJITWM (Chin) 2004;24(5):439
文摘Six patients treated with human leukocyte antigen (HLA)-mismatched bone marrow transplantation (BMT) suffered from grade I to IV acute graft-versus-host disease (aGvHD) after engrafting. Up to date, 4 patients with grade I to II GvHD have lived for over 2920, 910, 740 and 680 days, respectively. Two other patients died of grade IV hyperacute GvHD. The results seem to indicate that patients in mismatched BMT have a high incidence of aGvHD within a month. The severity of aGvHD is positively correlated with the degree of HLA mismatching. The higher the degree of mismatch of HLA, the earlier and the more severe the aGvHD occurrs. The cutaneous lesion of the patient with GvHD is severe and of ten complicated by mucositis. Lethal hyperacute GvHD must be considered when a patient shows following signs at beginning: (1) The symptoms appear early (within 2weeks) ;(2) peripheral white blood cell count does not recover (<0. 5×109/L) to normal; and (3) high fever persists. In the epidermal ultrastructure of patients, besides acantholysis, autophagic degeneration of keratinocytes,and satellite cell dyskeratosis, there were scattered necrotic keratinocytes, breaking and thickening of basal membrane and presence of a lot of pigment in the intercellular space. These imply that the ultrastructural damages in the skin of patients with aGvHD after mismatched transplantation are more severe than after matched ones.
文摘Hematopoietic syndrome of acute radiation syndrome(h-ARS)is an acute illness resulted from the damage of bone marrow(BM)microenvironment after exposure to radiation.Currently,the clinical management of h-ARS is limited to medication-assisted treatment,while there is still no specific therapy for the hematopoietic injury from high-dose radiation exposure.Our study aimed to assemble biomimetic three-dimensional(3D)BM microniches by co-culture of hematopoietic stem and progenitor cells(HSPCs)and mesenchymal stem cells(MSCs)in porous,injectable and viscoelastic microscaffolds in vitro.The biodegradable BM microniches were then transplanted in vivo into the BM cavity for the treatment of h-ARS.We demonstrated that the maintenance of HSPCs was prolonged by co-culture with MSCs in the porous 3D microscaffolds with 84μm in pore diameter and 11.2 kPa in Young’s modulus compared with 2D co-culture system.Besides,the minimal effective dose and therapeutic effects of the BM microniches were investigated on a murine model of h-ARS,which showed that the intramedullary cavity-injected BM microniches could adequately promote hematopoietic reconstitution and mitigate death from acute lethal radiation with a dose as low as 1000 HSPCs.Furthermore,the mRNA expression of Notch1 and its downstream target gene Hes1 of HSPCs were increased when co-cultured with MSCs,while the Jagged1 expression of the co-cultured MSCs was upregulated,indicating the significance of Notch signaling pathway in maintenance of HSPCs.Collectively,our findings provide evidence that biomimetic and injectable 3D BM microniches could maintain HSPCs,promote hematopoiesis regeneration and alleviate post-radiation injury,which provides a promising approach to renovate conventional HSPCs transplantation for clinical treatment of blood and immune disorders.
文摘Objective: To observe the effect of Chinese herbal medicine in alleviating acute toxic adverse effect of radiotherapy and on growth of stromal cells in bone marrow. Methods: Seventy two patients with nasopharyngeal carcinoma (NPC) were randomly divided into two groups. Radical radiotherapy was applied to both groups. In the radiotherapeutic period, to the 36 patients in the treated group, Yiqi Huoxue Yangyin Recipe (YHYR) was given additionally by oral taking and compressing on radiation area, and to the 36 patients in the control group, vitamin B 12 solution was given for gargling or compressing. Experimental study was carried out in rats of two groups, irradiated with 5.0 Gy X ray and treated with YHYR or normal saline intraperitoneally, to observe the colony forming unit fibroblastoid (CFU F) in cultured bone marrow stromal cells (BMSC), taken from the rats at different time.Results: The oral mucomembranous radiation damage occurred in 47.2% of the treated group when the dose of radiation reached to 41.4±9.4 Gy, while in the control group, it was 91.7% when the dose reached to 30.9±8.9 Gy. The skin radiation damage occurrence rate in the two groups was 13.9% and 33.3% respectively when the dose of radiation reached to 50.2±5.6 Gy and 43.2±6.3 Gy respectively. Comparison of the two groups showed significant difference ( P <0.01), the radiation damage was significantly slighter in the treated group. Experimental study showed that the rats in the two groups were significantly different in occurrence and degree of bone marrow function inhibition, P <0.01. The numbers of CFU F in cultured BMSC of radiation damaged rats taken at respective different culture time were also significantly different between the two groups, P < 0.01 .Conclusion: YHYR could significantly reduce acute radiation damage of mucomembrane and skin, alleviate the inhibition on bone marrow function, and eliminate the injury of radiation on BMSC.
文摘目的:建立一个稳定可靠的异基因骨髓移植(allogeneic bone marrow transplantation,Allo-BMT)急性移植物抗宿主病(acute graft-versus-host disease,aGVHD)动物模型,为Allo-BMT中aGVHD研究提供理想的实验平台。方法:以雄性C57BL/6(H-2b)为供鼠,雌性BALB/C(H-2d)为受鼠,受鼠致死性全身照射(total body irradiation,TBI)(8.0Gy)预处理后,在移植物中混合不同比例的供鼠骨髓细胞和脾细胞以引起不同程度的aGVHD。根据存活期、外周血白细胞计数、临床表现及病理检查等判断aGVHD程度。结果:单纯异基因骨髓组只有部分小鼠出现aGVHD,75%的小鼠长期存活(>30d)。混合不同比例的供鼠骨髓细胞和脾细胞的Allo-BMT小鼠出现aGVHD的时间和程度均有差异,其中骨髓与脾细胞1.5:1或1:1混合组小鼠,均可在相对集中的时间内(8～15d)观察到典型的aGVHD临床和病理改变。结论:建立Allo-BMT aGVHD模型需要加入一定比例的脾细胞,供鼠骨髓与脾细胞1.5:1或1:1混合进行的Allo-BMT,可作为理想的aGVHD动物模型。
