Orloff M J, Macedo C, Macedo A, Greenleaf G E
Ann Surg. 1987 Sep;206(3):324-34. doi: 10.1097/00000658-198709000-00010.
To compare the long-term effectiveness of whole pancreas transplantation and pancreatic islet transplantation in controlling the metabolic disorders and preventing the kidney lesions of alloxan diabetes, metabolic and morphologic studies were performed in four groups of rats: (1) NC-116 nondiabetic controls; (2) DC-273 untreated alloxan-diabetic controls; (3) PDT-182 rats that received syngeneic pancreaticoduodenal transplants not long after induction of diabetes with alloxan; and (4) IT-92 rats that received an intraportal injection of at least 1500 and usually 2000 syngeneic pancreatic islets soon after induction of diabetes with alloxan. Each month for 24 months after diabetes was well established, body weight and plasma concentrations of glucose and insulin were measured, and five lesions were scored by light microscopy in 50 glomeruli and related tubules in each kidney by a "blind" protocol: glomerular basement membrane thickening, mesangial enlargement, Bowman's capsule thickening, Armanni-Ebstein lesions of the tubules, and tubular protein casts. There were progressive and highly significant increases in the incidence and severity of all five kidney lesions in the diabetic control rats compared with the nondiabetic control rats. No significant differences were found between the kidneys of Group PDT and those of Group NC, demonstrating that whole pancreas transplantation prevented all of the diabetic kidney lesions throughout the 2-year study period. In contrast, within 3-9 months after pancreatic islet transplantation and thereafter, the incidence and severity of the five diabetic kidney lesions were similar in Group IT and Group DC. Whole pancreas transplantation produced precise metabolic control of diabetes throughout the 24 months of study, whereas pancreatic islet transplantation did not accomplish complete metabolic control, particularly beyond the first several months after transplantation. The difference in the completeness of metabolic control achieved by the two types of transplants is the most likely explanation for their sharp difference in effectiveness in preventing diabetic nephropathy.
为比较全胰腺移植和胰岛移植在控制代谢紊乱及预防四氧嘧啶糖尿病肾损害方面的长期效果，对四组大鼠进行了代谢和形态学研究：(1) NC - 116非糖尿病对照组；(2) DC - 273未经治疗的四氧嘧啶糖尿病对照组；(3) PDT - 182大鼠，在四氧嘧啶诱导糖尿病后不久接受同基因胰十二指肠移植；(4) IT - 92大鼠，在四氧嘧啶诱导糖尿病后不久经门静脉注射至少1500个通常为2000个同基因胰岛。在糖尿病确诊后24个月内，每月测量体重、血糖和胰岛素的血浆浓度，并采用“盲法”对每个肾脏的50个肾小球及相关肾小管中的五种病变进行光镜评分：肾小球基底膜增厚、系膜增大、鲍曼囊增厚、肾小管的阿-埃氏病变及肾小管蛋白管型。与非糖尿病对照组大鼠相比，糖尿病对照组大鼠所有五种肾脏病变的发生率和严重程度均呈进行性且极显著增加。PDT组大鼠的肾脏与NC组大鼠的肾脏之间未发现显著差异，表明在整个2年研究期内全胰腺移植可预防所有糖尿病肾脏病变。相比之下，在胰岛移植后3 - 9个月及之后，IT组和DC组五种糖尿病肾脏病变的发生率和严重程度相似。在整个24个月的研究中，全胰腺移植实现了对糖尿病的精确代谢控制，而胰岛移植未实现完全的代谢控制，尤其是在移植后的最初几个月之后。两种移植方式在代谢控制完整性上的差异最有可能解释它们在预防糖尿病肾病有效性上的显著差异。
