일측 신장의 허혈-재관류 모델에서 신조직내 TGF-β, TNF-α, 및 Endothelin-1 유전자 발현에 관한 연구

신영태(Young Tai Shin),김종학(Jong Hak Kim),황평주(Pyeung Joo Hwang),이강욱(Kang Wook Lee),서광선(Kwang Sun Suh),구영선(Young Sun Koo),강민규(Min Kyu Kang) 대한신장학회 2000 Kidney Research and Clinical Practice Vol.19 No.1

N/A Although the exact pathogenetic mechanisms of the renal ischemia-reperfusion injury(I-R injury) have not been clearly elucidated yet, the reactive oxygen spe-cies(ROS) and mononuclear cell infiltration have been suggested to contribute to this renal injury process. The cytokines and growth factors produced by infiltrated leukocytes and renal parenchymal cells could accelerate the process of tissue damage by inducing cellular proliferation, fibrosis, and further recruitment of other inflammatory cells. The renin-angiotensin sys- tem(RAS) also has been suggested to be one of the most important mediators in the renal injury process of many animal models and human renal diseases. In order to evaluate the change of the levels of TNF-α, endothelin-l, and TGF-βgene expression in unilateral I-R injured renal cortical tissue, competitive RT-PCR was performed for the above mRNAs in Sprague-Dawley rats(60 minutes of ischemic time by non-traumatic vessel clamp and 24 hours of reperfusion). Also the plasma renin activity(PRA) and an-giotensin II(AII) level were measured at the time of sacrifice by radioimmunoassay. On the light miscroscopic examination, I-R injured renal cortical tissue showed typical findings of acute tubular necrosis, such as mononuclear ceU infiltration, necrosis, swelling and denudation of proximal tubular cells. Compared to control sham operated group, I-R injured group tissues showed significantiy increased level of TGF-β(p<0.05), endothelin-l(p<0.05) and TNF-α(p<0.05) gene expression in 24 hours after I-R renal injury. The levels of PRA and AIl were also significantly elevated compared to sham group(p< 0.05, p<0.05, respectively). In conclusion, we speculate that the early activation of RAS and elevated gene expression of TNF-α, endothelin and TGF-β of renal cortieal tissue may contribute to the early pathogenetic mechanism of I-R renal injury process.

일측 요관폐쇄에 의한 실험적 수신증에서 신조직내 MCP-1 및 TNF-α유전자 발현

나가량,황평주,김종학,구영선,강민규,서광선,이강욱,신영태 충남대학교 의과대학 지역사회의학연구소 1999 충남의대잡지 Vol.26 No.2

Early cellular and molecular derangements have been suggested as potential pivotal factors for the development of renal injury, such as interstitial fibrosis after the experimental hydronephrosis. Several recent studies have been demonstrating that one of the initial events taking place in the progressive renal injury process is the mononuclear cell infiltration in the glomeruli and tubulointerstitiuim. In order to evaluate the renal light microscopic findings as well as the renal cortical MCP-1 and TNF-α gene expressions which are modulating inflammatory process and the recruitment of mononuclear cells in many experimental models of renal injury, Sprague-Dawley rats underwent unilateral ureteral obstruction (UUO) and sham operation under the thiopental sodium anesthesia(50 mg/kg intraperitoneal injection). Three and 7 days after surgery, rats were sacrificed. By the competitive RT-PCR, the levels of TNF-α and MCP-1 mRNA in renal cortical tissues were measured. The magnitude of mononuclear cell infiltration and interstitial widening were evaluated by standard point counting method. The level of MCP-1 gene expression was significantly increased in UUO group compared to sham group at 3 and 7 days after surgery(UUO 3 days 8.99 ± 0.45, UUO 7 days 11.2 ± 0.26, sham 3 days 1.00 ± 0.08, sham 7 days 0.94 ± 0.05, p < 0.01, p < 0.01, mean ± SEM, respectively). The level of MCP-1 mRNA at 7 days after surgery was significantly higher than that at 3 days in UUO group. The TNF-α gene expression level of UUO group was also significantly higher than that of sham group at 3 and 7 days after surgery(UUO 3 days 1.73 ± 0.16, UUO 7 days 2.03 ± 0.21, sham 3 days : 1.00 ± 0.06, sham 7 days 1.09 ± 0.03, p < 0.01, p < 0.01, respectively). But there was no significant difference between the levels at 3 and 7 days after surgery in UUO group(p>0.05). On the light microscopic examination, the relative volume of interstitium (RVI) and the total count of infiltrated mononuclear cells(MCC) at 3 and 7 days after surgery in UUO group were also significantly higher than those of sham group(RVI ; UUO 7 days 14.9±1.0%,sham 6.0±0.7%, MCC; UUO 7days 34.0± 1.6, sham 3.7± 0.6, p < 0.01, p < 0.01, respectively). In conclusion, we speculated that the early up-regulation of MCP-1 and TNF-α genes of renal cortical tissue in this experimental hydronephrosis model is closely related to the mononuclear cell infiltration and tubulointerstitial fibrosis.

지속성 외래 복막투석 환자의 복막염

신영태,황평주,김종학,강민규,구영선,양종오,장윤경,이강욱 충남대학교 의과대학 지역사회의학연구소 1999 충남의대잡지 Vol.26 No.1

CAPD has established itself as an effective method maintaining the patients with end stage renal disease. CAPD peritonitis is one of the most important complication of peritoneal dialysis. We analyzed the incidence, pathogens, and outcome of the peritonitis, of the 95 patients who underwent CAPD at CNUH from January 1993 to July 1998. The result were as follows : 1) A total of 72 episodes of peritonitis occurred during this periods. The incidence of peritonitis were 0.64/patient/year. 2) The first episode of peritonitis was occurred within a year in 75%, within two year in 95.8%. 3) The rate of positive and negative culture were 27.8% and 72.2% respectively. Gram positive organisms were cultured in 60%, Gram negative organisms in 40%. S. aureus were most prevalent organisms(30%). 4) The cure rate were 83.3% in Gram positive organisms and 62.5% in negative organisms. 5) Peritoneal catheter were removed in 18 cases. Among them, 7 cases are due to peritonitis. In conclusion, improved technology and increasing patients' effort to careful management of catheter will reduce the incidence of peritonitis.

신이식에서 이식신의 생존분석

오선미,김종학,황평주,구영선,강민규,나기량,김종섭,김성숙,이강욱,신영태,설종구,배진선,손기섭 충남대학교 의과대학 지역사회의학연구소 1997 충남의대잡지 Vol.24 No.2

To investigate the prognostic factors for the survival of transplanted kidney in patients with end-stage renal failure, 59 cases of renal transplantation from September 1986 to Feburary 1997 in Chungnam National University Hospital were analyzed retrospectively. The results were as follows: 1)The mean age of recipients was 33.8 years and that of doners was 38.9 years. The male to female ratio of recipients was 2.5:1, and that of donors was 1.03:1 2) Living related donore(LRD) were 79.6% and living non-related donors were 20.3%. The HLA-identical donors(ID) in LRD were 18.7% and HLA-haploidentical donors(HID) were 61.0%. In living non-related donors(LNRD), mean matched HLA-AB antigens were 1.56 and mean matched HLA-DR antigens were 0.56. 3) The average 5-year patient survival fate was 94%, and average 5-year graft survival rate was 70%. The 5-year graft survival fate of HLA-ID was 100%, and those HLA-HID and LNR were 70% and 36% respectively. 4) Total 33 episodes of acute rejection were found in 45.8% of transplanted patients. The number of acute rejection episode did not show significant difference between LRD and LNRD(P > 0.05). There was no significant difference in MLC between two groups(p > 0.05). 5) In comparison between the 18 patients who lost their graft function in 5 years and 17 patients who are maintaining graft function for more than 5 years, MLC was significantly lower in patients with functioning graft than of patients with non-functioning graft (p < 0.05). The number of rejection episode was also lower in patients with functioning graft than that of the patients with non-functioning graft(p < 0.05). However, there were no significant difference in recepient and donor age and history of pre-transplantation donor specific transfusion between two groups. With the results above, we can speculate that adequate donor selection according to good matched HLA typing and low MLC is very important for graft survival in renal transplantation. Prevention and treatment of acute rejection in renal transplantation is also na important factor for graft survival.

부분 신절제 백서모델에서 Angiotensin Converting Enzyme Inhibitor 및 Angiotensin II ATI 수용체 길항제가 Plasma Renin Activity 및 Angiotensin II level에 미치는 영향

김종학,구영선,강민규,황평주,나기량,이강욱,서광선,신영태 충남대학교 의과대학 지역사회의학연구소 1999 충남의대잡지 Vol.26 No.1

Renin-angiotensin-system(RAS) has been thought to have a pivotal role in renal injury mechanism. Many reports state that the inhibition of RAS prevents the progression of renal disease in 5/6 nephrectomized rats as a typical chronic renal failure model. Angiotensin converting enzyme inhibitor blocks the conversion from Angiotensin I to Angiotensin Ⅱ (A-Ⅱ ), and ATI RA inhibits the action of A-Ⅱ at the level of AT1 receptor. Therefore the PRA and A-Ⅱ level may be influenced independently by each treatment modality with these drugs. In this study, the influence of long term treatment with ACEI or AT1RA in these models on systolic blood pressure, PRA, and A-Ⅱ level was evaluated. Male Sprague-Dawley rats weighing 270-300 grams were anesthesized with thiopental sodium(50 mg/kg) and underwent right nephrectomy and partial(approximately two thirds) infarction of the left kidney by ligation of two-three segmental arterial branches. The rats were divided into four groups : sham group, control group, 5/6 subtotal nephrectomized and ACEI treated group (enalapril 100 mg/L in drinking water), 5/6 subtotal nephrectomized and ATIRA treated group (losartan, 200 mg/L in drinking water). They were treated for twelve weeks. In the twelve weeks, both groups treated with ACEI and AT1RA ingestion demonstrated a significant decrease in systolic blood pressure(165±23 vs. 132±9, mmHg, control vs. ACEI, M±SEM, p<0.05, 165±23 vs. 124±7 mmHg, control vs. ATIRA, M±SEM, p<0.01) compare to the control group. In both group treated with ACEI and AT1RA showed a significant increase in PRA(ACEI ; 7.2±2.9, AT1RA ; 4.7±0.4, control ; 2.7±1.1, sham ; 2.7±1.4, ng/ml/hr, ACEI vs. control and sham, M±SEM, p<0.05). However no significant differences were found in the sham vs. control(p>0.05), and in ACEI vs. control. The plasma A-II level was significantly increased in AT1RA treated group compared to sham and ACEI treated group(2,753±543 vs. 484±169.3, ng/ ml, AT1RA vs. Sham, p<0.01). In conclusion, treatment with ACEI and AT1RA for twelve weeks normalized systolic blood pressure, proteinuria and increased PRA compared to the control group; whereas plasma A-II level was increased only by AT1RA treatment.

혈청 HBsAg 양성인 사구체신염의 임상상 및 신조직 소견

신영태,구영선,강민규,황평주,김종학,이강욱,서광선 충남대학교 의과대학 지역사회의학연구소 1999 충남의대잡지 Vol.26 No.1

Hepatitis-B-associated glomerulonephritis is one of the immunologically mediated disorders associated with chronic Hepatitis B virus(HBV) infection. The frequency of HBsAg infection has been high in East Asia and it is one of the most important etiologic factors of the secondary glomerulonephritis. We reviewed the clinical and pathologic features of 29 patients with glomerulonephritis and HBs antigenemia, who were admitted to Chungnam National University Hospital from January 1988 to Febuary 1999. The results were as follows : 1) The average age of the patients was 33.8±10.4(mean±SD) and male to female ratio was 3.8. Proteinuria was present in 27 patients(93%), hematuria in 20 patients(69%) and hypertension in 17 patients(59%). Two patients(7%) manifested with renal insufficiency and 8 patients(28%) with nephrotic syndrome. 2) Renal pathology revealed membranous nephropathy(41%), membranoproliferative glomerulonephritis(21%), mesangial proliferative glomeulonephritis(21%), minimal change nephritis (14%) and focal segmental glomerulonephritis(3%). 3) The pathologic findings of liver were chronic active hepatitis(68%), chronic persistent hepatitis(38%) and liver cirrhosis(8%). 4) During the follow-up period(average:49.4 months), 7 patients(68%) presented persistent proteinuria, 5 patients(21%) progressed to renal failure and 2 patients(8%) resolved clinically. 5) The treatment was done with prednisolone to 3 patients, and with alpha-interferon to 3 patients. One patient treated with prednisolone resolved clinically, but this resolution did not coincide with disappearance of the hepatitis B antigens.

반월상 사구체신염의 임상적 고찰

신영태,황평주,장윤경,양종호,구영선,강민규,김종학,나기량,이강욱,서광선 충남대학교 의과대학 지역사회의학연구소 1998 충남의대잡지 Vol.25 No.1

The crescentic glomerulonephritis is a pathologic term which show glomerular destruction due to crescent composed of cellular and/or fibrotic tissue. If not treated aggressively, clinical picture of renal failure developing over weeks or months. So, it is meaningful to know which factors influence on outcome of this disease. We reviewed renal biopsies which had showed crescent more than half of glomeruli for the period March 1983 to March 1998 at Chugnam National University Hospital. We reviewed these cases about clinical features, laboratory findings, renal biopsy findings, management and outcome of patients retrospectively. We grouped these patients to "progress", improve", and "stable" by change in serum atinine level during follow up periods. The results were as follows : 1) The total numbers of patients were 13, the male patients were 6 and the female were 7. The mean age was 43.7+17. 1years. 2) The causes of crescentic glomerulonephritis were IgA nephropathy(4 patients), systemic lupus erythematosus(2 patients), Henoch-Scho"nlein purpura(1 patient), Wegener's Granulomatosis(1 patient), and primary crescentic glomerulonephritis(5 patients). 3) In outcome of patients, 7 of all patients were progress(53.8%), 1 patient was improve, 5 patients were stable. In disease entity, IgA nephropathy, Henoch-Scho"nlein purpura and primary crescentic glomerulonephritis type 1 have poor prognosis. SLE and Wegener's Granulomatosis 4) Five patients had oliguria. They showed lower hemoglobin level, higher ESR, serum BUN, creatinine and potasseum level, more crescent formation, more severe tubular atrophy and interstitial fibrosis in pathologic findings than non-oliguric patients. But outcome of the patent with or without oliguria was not different. In conclusion, factors indicating poor prognosis of crescentic glomerulonephritis were severe tubular atrophy and interstitial fibrosis in pathology.

신증후성 출혈열(HFRS)의 임상 양상에 관한 고찰

강민규,황평주,김종학,나기량,이강욱,신영태 충남대학교 의과대학 지역사회의학연구소 1998 충남의대잡지 Vol.25 No.2

Hemorrhagic fever with renal syndrome(HFRS) is an acute viral disease characterized by fever, cardiovascular instabilities, hemorrhagic manifestation and renal failure. Eighty-eight cases of HERS who were admitted to Chung-Nam National University Hospital from July 1988 to December 1997 were analysed from the stand-point of clinical and laboratory findings. The results were as follows. 1. The months of peak incidence were November and December. 2. The most frequent chief complains on admission were fever and chill, abdominal pain, nausea and vomiting, myalgia and headache, respectively. 3. The clinical stage on admission were oligouric(42 cases), febrile(22 cases), hypotensive(5 cases) and diuretic(3 cases) phase, respectively. 4. In laboratory analysis, leukocytosis, thrombocytopenia and proteinuria were observed in most of the case. 5. The infection rate of Leptospirosis and Scrub typhus in 72 HFRS patients was 13.9%(8 cases and 2 cases). 6. The mortality rate was 4.2% anti the cause of death were shock(2cases) and pulmonary hemorrhage(1 case)

다낭신 환자에서 발생한 급성 신피질 괴사 1예

강민규,김종학,이강욱,신영태,나기량,황평주,강정현,구영선 대한신장학회 1999 Kidney Research and Clinical Practice Vol.18 No.4

Acute cortical necrosis is a rare cause of the acute renal failure. It is frequently associated with complications of pregnancy. The renal biopsy is the key of diagnosis of these disease. However, the contrast enhanced CT scan can be a tool for the diagnosis of acute renal cortical necrosis, because of its noninvasiveness and constant findings(enhancement of subcapsular rim, nonenhancement of the renal cortex, enhancement of medulla, and lack of excretion of contrast media to the collecting system). This is a case of acute renal cortical necrosis diagnosed by CT scan. She had an anuria for 16 days and feature of hemolytic uremic syndrome and polycystic kidney.

성인 미세변화 신증후군의 임상상

김종학,김종섭,서광선,이강욱,김성숙,신영태,빈기태,나기량,오선미,황평주 대한신장학회 1998 Kidney Research and Clinical Practice Vol.17 No.1