本文選題：rhMG53 + PTRF�。� 參考：《第三軍醫(yī)大學(xué)》2013年碩士論文

【摘要】：內(nèi)臟器官是機(jī)體各項(xiàng)生命活動(dòng)的參與者和維持者。嚴(yán)重?zé)齻螅毙缘娜毖毖�、炎癥因子等因素，都會(huì)造成機(jī)體內(nèi)臟器官的損傷。內(nèi)臟器官受損，特別是多臟器功能損傷是燒傷病情加重、并發(fā)癥發(fā)生以及死亡率增加的重要特征。加強(qiáng)重要內(nèi)臟損傷的防治和促進(jìn)受損臟器早日修復(fù)與重建是提高救治成功率和大幅度降低死亡率的關(guān)鍵。嚴(yán)重?zé)齻�，由于臟器本身存在肉眼難辨的缺血性損害，加之這類損傷范圍廣，累計(jì)器官多，發(fā)病機(jī)制復(fù)雜、隱蔽以及缺乏有效的促修復(fù)措施，因而其損傷后的修復(fù)常不易引起人們的重視[1]。既往采取的各種措施，常常僅是針對發(fā)病機(jī)制的某一環(huán)節(jié)或減輕其損害程度，并不直接作用于修復(fù)細(xì)胞本身，故缺乏對臟器的主動(dòng)修復(fù)。因此，如何加速與促進(jìn)受損內(nèi)臟細(xì)胞的主動(dòng)修復(fù)有可能為防治多器官功能障礙綜合癥(multipleorgan dysfunction syndrome, MODS)、多臟器功能衰竭(multiple system organ failure,MSOF)發(fā)生以及提高救治成功率提供新的有效途徑，具體重要的理論意義和臨床應(yīng)用價(jià)值。 MG53(Mitsugumin53)，一個(gè)肌肉特有的TRIM家族蛋白，是細(xì)胞膜損傷修復(fù)的一個(gè)必不可少的組分。Ma等的研究表明，重組的人MG53(Recombinant HumanMitsugumin53，rhMG53)能夠治療肌營養(yǎng)不良癥以及以細(xì)胞膜損傷為發(fā)病機(jī)理的其他人類疾病。當(dāng)培養(yǎng)肌肉和非肌肉細(xì)胞的培養(yǎng)液中存在rhMG53時(shí)，rhMG53能夠識別細(xì)胞膜損傷信號，進(jìn)而提高這些細(xì)胞的膜修復(fù)能力。小鼠動(dòng)物實(shí)驗(yàn)研究表明，通過各種途徑(肌內(nèi)、靜脈、皮下)給予rhMG53，都能夠提高骨骼肌細(xì)胞膜修復(fù)能力，同樣也能一定程度上改善肌營養(yǎng)不良癥的組織病理變化[2]。 因此我們推測，機(jī)體嚴(yán)重燙傷后，通過外源性的rhMG53治療，可能對燙傷造成的各種臟器損傷起到一定的修復(fù)作用，改善臟器功能，提高生存率。本研究以30%的Ⅲ度燙傷小鼠為模型，觀察靜脈注射rhMG53對重度燒傷小鼠生存率和臟器組織的保護(hù)作用的影響，及其可能的機(jī)制。 研究內(nèi)容和方法: 1. MG53對30%Ⅲ°燙傷小鼠死亡率影響及臟器病理改變的實(shí)驗(yàn)研究 1)小鼠Ⅲ°燒傷模型的制作 使用YLS-Q5超級臺式溫控燙傷儀致傷Bal b/c小鼠，通過溫度和時(shí)間兩個(gè)因素控制燙傷深度。使用致傷溫度為90℃，自重500g，燙頭直接2cm恒溫金屬燙頭垂直接觸小鼠皮膚6s，8s，10s，經(jīng)HE染色觀察燒傷皮膚組織學(xué)改變，確定小鼠Ⅲ°燒傷模型的制作條件。 2)MG53對30%Ⅲ°燙傷小鼠死亡率影響及臟器病理改變的研究 實(shí)驗(yàn)前分裝外源性rhMG53蛋白。16只20g左右的雄性Bal b/c小鼠，隨機(jī)分兩組，為MG53實(shí)驗(yàn)組及BSA對照組，分別制作30%Ⅲ°燙傷面積，傷后予以腹腔注射2.5ml乳酸鈉林格注射液，燙傷后0.5h，燙傷后6.5h，分別通過尾靜脈注射外源性rhMG53蛋白及BSA蛋白，傷后每6小時(shí)記錄小鼠死亡數(shù)目至傷后48小時(shí)，統(tǒng)計(jì)死亡率。傷后48小時(shí)存活的小鼠心臟灌注，取小鼠的心，肝，脾，肺，腎，小腸，結(jié)腸，腦，肌肉，皮膚，胃組織，4%多聚甲醛固定，24h組織脫水，石蠟包埋、切片，行蘇木精-伊紅(HE)染色，顯微鏡下觀察各組組織損傷情況。 3)重度燙傷小鼠腎臟損傷的評估 ①重度燙傷小鼠腎小管壞死程度的評分 隨機(jī)選取每只小鼠腎臟切片一張，并在顯微鏡下隨機(jī)選取20個(gè)視野觀察，根據(jù)腎小管的壞死程度，采用Erdogan等的半定量病理評估法評分：評分越高說明腎小管壞死越嚴(yán)重，0分：正常腎臟；1分：最少壞死(5%腎小管壞死)；2分：輕度壞死(5%～25%腎小管壞死)；3分：中度壞死(25%～75%腎小管壞死)；4分：重度壞死(75%的腎小管壞死)。分析的實(shí)驗(yàn)結(jié)果以(x±s)表示，采用Microsoft Excel軟件及SPSS13.0統(tǒng)計(jì)軟件行統(tǒng)計(jì)分析，P 0.05為差異有統(tǒng)計(jì)學(xué)意義。 ②免疫組織化學(xué)SP法檢測重度燙傷小鼠腎臟中KIM-1的表達(dá) 取前面實(shí)驗(yàn)小鼠的腎臟石蠟切片，分MG53實(shí)驗(yàn)組及BSA對照組，，每組選取4張切片，使用腎損傷分子-1(Kidney Injury Molecule-1，KIM-1)多克隆抗體行免疫組化(IHC)染色，顯微鏡下觀察各組腎臟中KIM-1的表達(dá)情況；每張切片隨機(jī)選取5個(gè)視野，顯微鏡下拍照，拍照后，IPP軟件半定量分析，分析的實(shí)驗(yàn)結(jié)果以(x±s)表示，采用Microsoft Excel軟件及SPSS13.0統(tǒng)計(jì)軟件中的獨(dú)立樣本t檢驗(yàn)進(jìn)行統(tǒng)計(jì)分析，P 0.05為差異有統(tǒng)計(jì)學(xué)意義。 2．通過尾靜脈注射的外源性rhMG53蛋白在體內(nèi)的分布及重度燙傷后PTRF體內(nèi)表達(dá)的變化 1)免疫組化方法檢測外源性rhMG53蛋白在小鼠體內(nèi)的分布 取前面實(shí)驗(yàn)小鼠臟器的石蠟切片，使用MG53多克隆抗體，分別進(jìn)行免疫組織化學(xué)染色，以心肌及骨骼肌表達(dá)內(nèi)源性MG53組織作陽性對照，觀察其他臟器中外源性rhMG53分分布，顯微鏡下觀察，拍照。 2)免疫組化方法檢測正常小鼠及重度燙傷小鼠體內(nèi)的PTRF的表達(dá) 取正常小鼠及重度燙傷小鼠腎臟的石蠟切片，使用PTRF多克隆抗體，分別進(jìn)行免疫組化，觀察重度燙傷后，小鼠體內(nèi)PTRF表達(dá)的變化，顯微鏡下拍照，拍照后，IPP軟件半定量分析，分析的實(shí)驗(yàn)結(jié)果以(x±s)表示，采用Microsoft Excel軟件及SPSS13.0統(tǒng)計(jì)軟件中的獨(dú)立樣本t檢驗(yàn)進(jìn)行統(tǒng)計(jì)分析，P 0.05為差異有統(tǒng)計(jì)學(xué)意義；繼續(xù)取重度燙傷小鼠小腸及皮膚石蠟切片，性免疫組化染色，觀察PTRF的表達(dá)情況。 實(shí)驗(yàn)結(jié)果: 1. MG53對30%Ⅲ°燙傷小鼠死亡率影響及臟器病理改變的實(shí)驗(yàn)研究 1)小鼠Ⅲ°燒傷模型的制作 在自然狀態(tài)下，使用燙頭直接接觸小鼠皮膚8s，壓力為500g，燙頭溫度為90℃時(shí)，組織學(xué)顯示皮膚各層、皮下附件及皮下脂肪組織均發(fā)生凝固性壞死，無完整的細(xì)胞結(jié)構(gòu)，真皮內(nèi)膠原腫脹變形，符合Ⅲ°燒傷組織學(xué)改變。 2)MG53對30%Ⅲ°燙傷小鼠死亡率影響及臟器病理改變的研究 MG53給藥組傷后48h的死亡率為25%，BSA組傷后48h的死亡率為37.5%，MG53給藥組死亡率低于BSA對照組，但統(tǒng)計(jì)學(xué)Kaplan-Meier分析，P值＞0.05，無統(tǒng)計(jì)學(xué)差異；HE染色結(jié)果顯示，嚴(yán)重?zé)齻笮∈蟮男�、肝、脾、肺、胃、小腸、結(jié)腸、皮膚、肌肉、腦組織等臟器均有不同程度的組織學(xué)變化，但MG53給藥組和BSA對照組在上述多數(shù)組織中無明顯的差別，有明顯差別的臟器是腎臟。組織切片顯示MG53}f藥組的腎臟近曲小管和遠(yuǎn)曲小管上皮細(xì)胞濁腫變性、壞死脫落以及腎間質(zhì)炎癥細(xì)胞浸潤方面較對照組有明顯改善，腎小球無明顯變化。 3)重度燙傷小鼠腎臟損傷的評估 ①重度燙傷小鼠腎小管壞死程度的評分 MG53給藥組的Erdogan半定量病理評分顯著低于BSA對照組腎小管病理損傷評分(P0.0001)。 ②免疫組織化學(xué)SP法檢測重度燙傷小鼠腎臟中KIM-1的表達(dá) 各組腎臟KIM-1免疫組化結(jié)果顯示：腎皮質(zhì)髓質(zhì)的損傷部位均可見KIM-1的表達(dá)，且表達(dá)量隨腎臟損傷范圍及程度的增加而成明顯升高趨勢。顯微鏡下觀察結(jié)果顯示，MG53給藥組小鼠腎臟的KIM-1表達(dá)明顯弱于BSA對照組，而在用PBS代替一抗的損傷腎臟中，沒有發(fā)現(xiàn)陽性染色；通過IPP軟件分析各組小鼠KIM-1表達(dá)的平均光密度顯示，MG53給藥組平均光密度OD值顯著低于BSA對照組，差異有明顯的統(tǒng)計(jì)學(xué)意義(P0.0001)。 2．通過尾靜脈注射的外源性rhMG53蛋白在體內(nèi)的分布及重度燙傷后PTRF體內(nèi)表達(dá)的變化 1)免疫組化方法檢測外源性rhMG53蛋白在小鼠體內(nèi)的分布 免疫組化結(jié)果顯示，沒有給予rhMG53的小鼠體內(nèi)，內(nèi)源性MG53主要分布在心肌和骨骼肌，可見骨骼肌細(xì)胞胞漿和心肌細(xì)胞呈強(qiáng)陽性染色。除心肌和骨骼肌外，其它組織均為陰性。在rhMG53給藥組，小鼠的rhMG53主要分布于部分腎皮質(zhì)腎小管上皮細(xì)胞和部分腎髓質(zhì)腎小管上皮細(xì)胞，并且強(qiáng)陽性染色主要集中于損傷嚴(yán)重的區(qū)域，而對照組在這些部位未見陽性細(xì)胞。另外MG53實(shí)驗(yàn)組小鼠的肺臟中，發(fā)現(xiàn)大量rhMG53的分布，且rhMG53主要分布于肺臟部分小靜脈內(nèi)皮細(xì)胞胞漿中，而其他組織中未見明顯陽性細(xì)胞。 2)免疫組化方法檢測正常小鼠及重度燙傷小鼠體內(nèi)的PTRF的表達(dá) 腎臟PTRF免疫組化結(jié)果顯示：正常小鼠腎臟和重度燙傷小鼠腎臟，皆可見大量的強(qiáng)陽性染色，且在腎臟的皮質(zhì)和髓質(zhì)都存在大量的強(qiáng)陽性區(qū)域。顯微鏡下初步觀察結(jié)果顯示，兩組腎臟PTRF的表達(dá)無明顯差別，而在用PBS代替一抗的腎臟中，沒有發(fā)現(xiàn)陽性染色；通過IPP軟件分析各組小鼠PTRF表達(dá)的平均光密度OD值，結(jié)果顯示，正常小鼠腎臟平均光密度OD值與重度燙傷小鼠相比，無明顯的統(tǒng)計(jì)學(xué)差異(P=0.890)；另外小鼠的小腸及皮膚中，皆有PTRF的弱陽性表達(dá)，較腎臟相比較，陽性區(qū)域的面積及染色強(qiáng)度明顯較弱。 實(shí)驗(yàn)結(jié)論：動(dòng)物實(shí)驗(yàn)研究發(fā)現(xiàn)，尾靜脈注射rhMG53蛋白能夠選擇性到達(dá)PTRF的高表達(dá)的腎臟。尾靜脈注射rhMG53蛋白能夠降低30%Ⅲ°燙傷小鼠早期死亡的發(fā)生，并改善腎臟的病理損傷情況。上述研究提示，嚴(yán)重?zé)齻笸庠葱詒hMG53蛋白能夠通過腎臟局部的PTRF早期對腎臟起到保護(hù)作用。
[Abstract]:Visceral organs are the participants and maintainers of various life activities. After severe burns, acute ischemic anoxia, inflammatory factors and other factors will cause the injury of the internal organs of the body. The damage of the viscera, especially the injury of multiple organs, is the important feature of the aggravation of the burn condition, the complication and the increase of mortality. The prevention and treatment of visceral injury and the promotion of early repair and reconstruction of damaged organs are the key to improve the success rate and reduce the mortality of the injured organs. After severe burns, the viscera itself has an ischemic damage to the naked eye. In addition, the scope of this kind of injury is wide, the accumulative organs are many, the pathogenesis is complex, and the effective measures for promoting the repair are lack. Therefore, the repair after the injury is often not easy to cause people to pay attention to the various measures taken by [1]., often only for a certain link of the pathogenesis or to reduce the degree of damage, it does not directly affect the repair of the cell itself, so it lacks the active repair of the viscera. Therefore, how to accelerate and promote the active repair of the damaged viscera cells. It is possible to provide a new effective way to prevent multiple organ dysfunction syndrome (Multipleorgan dysfunction syndrome, MODS), multiple organ failure (multiple system organ failure, MSOF) and to improve the success rate of treatment. It is of important theoretical significance and clinical application value.
MG53 (Mitsugumin53), a muscle specific TRIM family protein, is an essential component of cell membrane damage repair,.Ma and other studies suggest that the recombinant human MG53 (Recombinant HumanMitsugumin53, rhMG53) can treat muscular dystrophy and other human diseases with cell membrane damage as the pathogenesis. When cultured and not, the muscle and other human diseases are developed. When rhMG53 is present in the culture fluid of the muscle cells, rhMG53 can identify the signal of cell membrane damage and improve the membrane repair ability of these cells. Experimental study in mice shows that rhMG53 can be improved by various pathways (intramuscular, venous, subcutaneous), and it can also improve muscle nutrition to some extent. Histopathological changes in adverse events [2].
Therefore, we speculate that after severe scald, exogenous rhMG53 therapy may play a certain role in repairing the various organs damage caused by scald, improving the function of the organs and improving the survival rate. In this study, a model of 30% degree scald mice was used to observe the survival rate and organs of severely burned mice by intravenous injection of rhMG53. The effect of protection and its possible mechanisms.
Research contents and methods:
Effect of 1. MG53 on mortality and visceral pathological changes in 30% ~ 3 degree scalded mice
1) the production of mouse model of third degree burn
The Bal b/c mice were injured by the YLS-Q5 Super Table temperature control scald instrument, and the scald depth was controlled by two factors of temperature and time. The injury temperature was 90 C, the weight of self weight was 500g, the mouse skin was directly exposed to 6S, 8s, 10s with the scald 2cm constant temperature metal perm. The histological changes of burn skin skin were observed by HE staining, and the production of the model of the mice was determined. Conditions.
2) effect of MG53 on mortality and visceral pathological changes in 30% ~ 3 degree scalded mice
Before the experiment, the male Bal b/c mice were divided into two groups of exogenous rhMG53 protein.16 only about 20g, which were randomly divided into two groups: MG53 experimental group and BSA control group. The area of 30% degree scald was made, 2.5ml Sodium Lactate Ringer's Injection was injected intraperitoneally after injury, 0.5h after scald, 6.5h after scald, and exogenous rhMG53 protein and BSA protein were injected through the tail vein. Every 6 hours after injury, the death number of mice was recorded to 48 hours after injury, and the death rate was recorded. The heart, liver, spleen, liver, spleen, lung, kidney, intestine, colon, brain, muscle, skin, stomach tissue, 4% polyformaldehyde fixed, 24h tissue dehydration, paraffin embedding, HE staining and microscopic observation under microscope were observed. Injury in the group.
3) evaluation of renal injury in severely scalded mice
Score of renal tubular necrosis in severely scalded mice
Randomly selected one slice of each mouse kidney and randomly selected 20 visual fields under the microscope. According to the necrosis degree of renal tubules, Erdogan and other semi quantitative pathological evaluation were used. The higher the score, the more serious the renal tubular necrosis was, the 0 points: the normal kidney; 1 points: the least necrosis (5% renal tubular necrosis); 2 points: mild necrosis. (5% ~ 25% renal tubular necrosis); 3: moderate necrosis (25% to 75% renal tubular necrosis); 4 points: severe necrosis (75% of renal tubular necrosis). The results of the analysis were (x + s), and the statistical analysis was performed by Microsoft Excel software and SPSS13.0 statistical software, and P 0.05 was statistically significant.
Immunohistochemical SP method was used to detect the expression of KIM-1 in kidney of severely scalded mice.
The paraffin section of the kidney of the experimental mice was taken, divided into 4 sections of MG53 experimental group and BSA control group, each group selected 4 slices, using Kidney Injury Molecule-1, KIM-1 polyclonal antibody and immunohistochemistry (IHC) staining. The expression of KIM-1 in the kidneys of each group was observed under microscope; each slice was randomly selected for 5 fields of vision and under microscope. After taking pictures and taking pictures, the IPP software is semi quantitative analysis, the results of the analysis are (x + s), and the statistical analysis is carried out by the t test of independent samples in Microsoft Excel software and SPSS13.0 statistics software. P 0.05 has statistical significance.
2. the distribution of exogenous rhMG53 protein through tail vein in vivo and the changes of PTRF expression after severe scald.
1) immunohistochemical method was used to detect the distribution of exogenous rhMG53 protein in mice.
The paraffin section of the viscera of the previous experimental mice was taken with MG53 polyclonal antibody and immunohistochemical staining was performed respectively. The expression of endogenous MG53 tissues expressed in myocardium and skeletal muscle was used as positive control, and the source rhMG53 distribution in other organs was observed and observed under microscope, and photographed.
2) immunohistochemical method was used to detect the expression of PTRF in normal mice and severely scalded mice.
The paraffin section of normal mice and severely scalded mice was taken by using PTRF polyclonal antibody and immunohistochemistry. The changes of PTRF expression in the body of the mice were observed after severe scald. Under the microscope, the IPP software was semi quantitative analysis. The results of the analysis were (x + s), and the Microsoft Excel software and SPSS13.0 statistics were used. The independent sample t test in the software was statistically analyzed, and the difference was statistically significant in P 0.05, and the paraffin section of small intestine and skin in severe scalded mice was continued, and the expression of PTRF was observed by sexual immunohistochemical staining.
Experimental results:
Effect of 1. MG53 on mortality and visceral pathological changes in 30% ~ 3 degree scalded mice
1) the production of mouse model of third degree burn
Under natural condition, the skin 8s was directly exposed to the skin of mice with a perm head, the pressure was 500g, and the perm temperature was 90 C. The histology showed that all layers of skin, subcutaneous appendages and subcutaneous adipose tissue were all coagulated necrosis, without complete cell structure, the swelling and deformation of the collagen in the dermis, and the histological change of the third degree burn.
2) effect of MG53 on mortality and visceral pathological changes in 30% ~ 3 degree scalded mice
The mortality of 48h after injury in MG53 group was 25%, the mortality of 48h after injury in group BSA was 37.5%, and the mortality of MG53 administration group was lower than that of BSA control group, but statistically Kaplan-Meier analysis, P value was > 0.05, no statistical difference, and HE staining results showed that the heart, liver, spleen, lung, stomach, intestines, colonic, skin, muscle and brain tissues of the mice after severe burns were found. There was no obvious difference between the MG53 administration group and the BSA control group, but the visceral organs with distinct differences were renal. The tissue section showed that the renal proximal convoluted tubule and the distal tubule epithelial cells in the MG53}f drug group were cloudy and swollen, necrosis and exfoliation and the infiltration of renal interstitial inflammatory cells were more obvious than those in the control group. There was no significant change in the glomeruli.
3) evaluation of renal injury in severely scalded mice
Score of renal tubular necrosis in severely scalded mice
The Erdogan semi quantitative pathological score in the MG53 administration group was significantly lower than that in the BSA control group (P0.0001).
Immunohistochemical SP method was used to detect the expression of KIM-1 in kidney of severely scalded mice.
The results of KIM-1 immunohistochemistry in each group showed that the expression of KIM-1 was visible in the injured parts of the medulla of the renal cortex, and the expression was obviously increased with the increase of renal damage range and degree. Under the microscope, the expression of KIM-1 in the kidney of the MG53 administration group was significantly weaker than that of the BSA control group, and the PBS was used instead of the one resistance. No positive staining was found in the injured kidneys, and the average optical density of KIM-1 expression in each group was analyzed by IPP software. The average optical density of MG53 in the group was significantly lower than that of the BSA control group, and the difference was statistically significant (P0.0001).
2. the distribution of exogenous rhMG53 protein through tail vein in vivo and the changes of PTRF expression after severe scald.
1) immunohistochemical method was used to detect the distribution of exogenous rhMG53 protein in mice.
The results of immunohistochemistry showed that the endogenous MG53 was mainly distributed in the myocardium and skeletal muscle in the mice without rhMG53, and the cytoplasm and myocardial cells of the skeletal muscle cells were strongly positive. All the other tissues were negative except for the myocardium and the skeletal muscle. In the rhMG53 administration group, the rhMG53 of the mice was mainly distributed in the epithelium of some renal cortex and renal tubules. Cell and partial renal medullary renal tubular epithelial cells, and strong positive staining mainly concentrated in the area of severe injury, but in the control group, no positive cells were found in these areas. In addition, a large number of rhMG53 were found in the lungs of the MG53 experimental group, and rhMG53 was mainly distributed in the small venous endothelial cell cytoplasm of the lungs and in other tissues. No obvious positive cells were found.
2) immunohistochemical method was used to detect the expression of PTRF in normal mice and severely scalded mice.
The renal PTRF immunohistochemical results showed that a large number of strong positive staining was found in kidney of normal mice and severely scalded mice, and a large number of strong positive regions were found in the cortex and medulla of the kidneys. Under the microscope, the results showed that the expression of PTRF in the two groups of kidneys had no obvious difference, but in the use of PBS instead of the kidney, no kidney was used. The average optical density o value of PTRF expression in each group was analyzed by IPP software. The results showed that the average optical density o value of normal mice kidney had no significant difference compared with that of severe scalded mice (P=0.890). In addition, there was a weak positive expression of PTRF in the small intestine and skin of mice, compared with the kidney. The area and dyeing strength of the region are obviously weak.
Experimental results: the experimental study found that the injection of rhMG53 protein in the tail vein can selectively reach the high expression of PTRF in the kidney. The injection of rhMG53 protein in the tail vein can reduce the occurrence of early death in 30% degree scald mice and improve the pathological damage of the kidney. The above study suggests that exogenous rhMG53 protein can pass after severe burns. Early renal PTRF plays a protective role in kidney.
【學(xué)位授予單位】：第三軍醫(yī)大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2013
【分類號】：R644

【參考文獻(xiàn)】

相關(guān)期刊論文 前4條

1 劉毅,薛曉東,賈赤宇,陳璧;恒溫恒壓電燙儀建立小鼠燙傷模型的實(shí)驗(yàn)研究[J];蘭州醫(yī)學(xué)院學(xué)報(bào);2001年01期

2 夏照帆;;燒傷后多臟器損傷及防治——燒傷新進(jìn)展之一[J];中華燒傷雜志;2006年03期

3 石艷;靳英麗;王艷晶;王大宇;李相軍;于曉艷;孫波;任立群;;KIM-1在UUO大鼠腎臟表達(dá)的研究[J];中國實(shí)驗(yàn)診斷學(xué);2010年10期

4 付小兵,盛志勇;進(jìn)一步重視和加強(qiáng)對嚴(yán)重創(chuàng)傷后內(nèi)臟缺血性損傷修復(fù)的研究[J];中國危重病急救醫(yī)學(xué);1999年06期

本文編號：1906309