OBJECTIVE To further explore the underlying mechanism of the association between IL-1 receptor antagonist（IL-lra）gene polymorphism and disease phenotypes，the functional significance of IL-1ra gene polymorphism in systemic lupus erythematosus（SLE）patients was studied．

METHODOLOGY This study included 13 SLE patients among whom 6 were of IL1RN2（-） genotype and 7 of IL1RN2（＋） genotype．The control group consisted of 4 healthy adults of IL1RN2（-） and 4 of IL1RN2（＋） who were matched in age and sex．The genotype was determined with PCR assay．Peripheral monocytes were collected and cultured with or without the stimulation of GM-CSF．Production of IL-1ra，IL-1α and IL-1β were measured with ELISA in the supernatant．

RESULTS Under static condition，no difference in the production of IL-1ra was found neither between the IL1RN2（＋） and IL1RN2（-）SLE patients（5.24±1.4 μg／L vs 6.01±1.19 μg／L，P＞0.05) nor between IL1RN2（＋） and IL1RN2（-） controls (6.39±1.80 μg／L vs 5.91±0.88 μg／L，P＞0.05)．But with the stimulation of GM-CSF，enhanced production of IL-1ra in peripheral monocytes was found in both IL1RN2（-）SLE patients and controls as compared to the IL1RN2（＋）SLE patients（24.00±3.30 μg／L vs 13.7±1.73 μg／L，P＜0.001)and controls（19.80±2.21 μg／L vs 9.01±1.52 μg／L，P＜0.001)．Enhanced production of IL-1α and IL-1β was observed in both IL1RN2（＋） and IL1RN2（-） SLE patients and controls．But no difference in LI-1α and IL-1β production was found among IL1RN2（＋）and IL1RN2（-）SLE patients and controls，neither in the static nor stimulated conditions．

CONCLUSION Carriers of IL1RN2(both SLE patient and healthy control)tend to have a lower capacity of producing IL-1ra with the stimulation of inflammatory factors than the non-carriers．These results add a functional link to the association of IL1RN2 allele to the server clinical inflammatory manifestations in SLE patients．

Key words IL-1-receptor antagonist gene polymorphism systemic lupus erythematosus

VARIATION OF INTRACELLULAR FREE CALCIUM CONCENTRATION IN ARISTOLOCHIC ACID I INDUCED APOPTOSIS IN LLC-PK1 CELLS AND INHIBITION OF APOPTOTIC DAMAGE BY LACIDIPINE

Gao Ruitong，Zheng Falei，Liu Yanxin，Zheng Dexian，Li Xuemei，Liu Yin

Peking Union Medical College Hospital，Institute of Basic Medical Sciences，Peking Union Medical College，Beijing，100730

OBJECTIVE To examine the changes of intracellular free calcium concentration（［Ca^2＋］_i）in aristolochic acid I（AAI） induced apoptosis in LLC-PK1 cells，and the effects of Lacidipine（a calcium antagonist）on the changes of ［Ca^2＋］_i and apoptosis induced by AAI．

METHODOLOGY LLC-PK1 cells were treated in different groups：（a）normal，without treatment；（b）with AAI alone（0.04 g／L）；（c）with Lacidipine alone（10，10²，10³ ng／L）；（d）with AAI（0.04 g／L）plus Lacidipine（10 or 10² or 10³ ng／L）．Mean［Ca^2＋］_i was measured by laser confocus microscopy using Fluo-3／AM staining．Light microscopy，Annexin-V-Flous apoptosis detection kit and flow cytometry using propidium iodiode staining were used to identify or quantify the apoptosis of LLC-PK1 cell．

RESULTS AAI-induced apoptosis of LLC-PK1 cells was found to be dose-dependent．Mean［Ca^2＋］_i was significantly higher in cells treated with AAI than that in normal cells (58.01±18.89 vs 22.66±4.78，P＜0.001)．In group treated with AAI plus Lacidipine （10² or 10³ng／L），mean［Ca^2＋］_i was significantly lower than that treated with AAI alone (35.47±10.16 ，28.55±12.85 vs 58.01±18.89，P＜0.001)．And the apoptotic cells ratios in group treated with AAI plus Lacidipine （10²，10³ ng／L）were also significantly lower than that treated with AAI alone（19.0%，27.8% vs 34.7%，P＜0.001）．

CONCLUSION The increase of ［Ca^2＋］_i in AAI-treated LLC-PK1 cells may be related to AAI-induced apoptosis．Lacidpine may reduce AAI-induced apoptosis by inhibiting increase of ［Ca^2＋］_i in LLC-PK1 cell．

Key words apoptosis aristolochic acid calcium antagonist

CHINESE HERB NEPHROPATHY：EXPERIENCE OF THREE CASES OF NEPHROTOXICITY CAUSED BY AKEBIA QUINATA

Yin Guang，Hu Weixin，Li Leishi

Research Institute of Nephrology，Jinling Hospital，Nanjing，210002

OBJECTIVE To report our experience of 3 cases of toxic nephropathy caused by Akebia Quinata （a Chinese herb）．

METHODOLOGY A retrospective study of 3 cases of Akebia Quinata nephrotoxicity was made．Clinical and pathological（of renal biopsy）data were collected and analyzed．

RESULTS All of the three patients were administered with one intake of Chinese herb medicine（Akebia Quinata，at dosage of 30g，10g，and 50g respectively）for the treatment of urinary stone．The early clinical manifestation included nausea，vomiting，hypokalaemia and metabolic acidosis．Renal manifestations of Akebia Quinata nephrotoxicity included non-oliguric acute renal failure，increased urinary excretion of lysosomes and N-acetyl-beta-D-glucosaminidase （NAGase），decreased urinary osmolarity，glucosuria and renal tubular acidosis．Pathological findings in renal biopsy included acute tubular necrosis，acute interstitial nephritis，a few interstitial infiltration of inflammatory cells，and minimal mesangial proliferative lesion in the glomeruli．In the follow-up of the patients，chronic increase in serum creatinine level was observed．

CONCLUSION Over dosage of Akebia Quinata may cause nephrotoxicity in patients with urinary stone．Unique clinical and pathological features were associated with Akebia Quinata nephrotoxicity．

Key words Akebia Quinata Toxic Nephropathy Toxication

EXPERIMENTAL STUDY OF ACUTE NEPHROTOXICITY INDUCED BY ARISTOLOCHIA MANSHURIENSIS KOM IN RATS

Qiu Qi，Liu Zhihong，Chen Huiping，Yang Junwei，Zheng Caihong，Li Leishi

Research Institute of Nephrology，Jinling Hospital，Nanjing 210002

OBJECTIVE To investigate the clinical features and pathological changes of acute nephrotoxicity induced by Aristolochia Manshuriensis Kom （AMK，a Chinese herb）in rats．

METHODOLOGY Experimental model of acute renal injury was established in the Sprague-Dawley rats with oral administration of decoction of AMK in a dosage of 60g／kg body weight for 5 consecutive days．Serum urea and creatinine levels，urinary activity of N-acetyl-beta-D-glucosaminidase（NAG），urinary protein，glucose，osmolality and volume were assayed on the day 0，2，4，6，8 of the experiment after acute renal injury．Renal histological examination was also performed．

RESULTS The important renal functional changes of nephrotoxicity due to AMK included azotemia，oliguria，proteinuria，glycouria，urinary hypoosmolality，and NAG enzymuria．Histopathological changes in the kidney