谷胱甘肽硫转移酶基因多态性与精子形成的研究进展

精子发生受到诸多有序基因的表达与调控,这些特异基因的遗传多态性可能影响精子的发生。谷胱甘肽硫转移酶是一组多功能同工酶,属于II相反应代谢的超家族酶系,其通过催化还原型谷胱甘肽与亲电物质发生轭合反应,降低该亲电物质的活性、加速其排泄,达到解毒的效果。研究发现,谷胱甘肽硫转移酶基因多态性与精子发生可能存在密切关系。     

马兜铃酸肾病研究进展

马兜铃酸肾病是近些年发现的药物性肾损害疾病 ,主要是指马兜铃酸引起的急、慢性肾小管 间质病变 ,可表现为急、慢性肾功能衰竭。本文就该病的由来、临床表现、发病机理、预防与治疗以及相关的中药作一综述。     

马兜铃酸肾病最新研究进展

近年来有关马兜铃酸肾病的研究又取得较多突破性进展,本文重点从马兜铃酸代谢酶学、致病机制以及与巴尔干肾病的联系等方面的最新研究进展进行综述,并为今后的研究提出了新的方向.     

马兜铃酸肾病的发病机制

马兜铃酸诱导的肾小管上皮细胞转分化、坏死或凋亡等诸多因素在马兜铃酸肾病的肾间质纤维化过程中起重要作用,其确切机制尚待进一步研究。     

马兜铃酸肾病发病机制的研究进展

含马兜铃酸（AA）类成分中药导致的肾损害--马兜铃酸肾病近年受到国内外医药学界的广泛关注，其确切发病机制尚未阐明。本文总结了国内外近年来有关马兜铃酸肾病发病机制的研究概况。     

谷胱甘肽转硫酶基因多态性与湖北汉族人群溃疡性结肠炎的关系

目的 探讨谷胱甘肽转硫酶(GSTs)基因多态性与湖北汉族人群溃疡性结肠炎(UC)的关系.方法 回顾性分析2002年8月至2009年12月武汉大学中南医院、武汉大学人民医院、华中科技大学附属同济医院和协和医院收治的270例湖北汉族UC患者(UC组)及同期623例健康体检者(对照组)的临床资料.根据病变范围将UC患者分为远端UC组(229例)和广泛UC组(41例);根据病变严重程度将UC患者分为轻中度组(237例)和重度组(33例).采用聚合酶链反应检测GSTM1和GSTT1的基因多态性、采用限制性片段长度多态性聚合酶链反应检测GSTP1的基因多态性,并对GSTs基因型进行判定.将含有157 bp片段和480 bp片段者分别定义为GSTM1(+)和GSTT1(+),而无相应的扩增产物者分别定义为GSTM1(-)、GSTT1(-).采用x2检验对数据进行分析.结果 UC组和对照组中GSTM1(-)、GSTT1(-)和GSTP1纯合子突变型基因型(Val/Val)的分布频率分别为70.7%(191/270)、64.8%(175/270)、48.9%(132/270)和41.7%(260/623)、47.2%(294/623)、34.3%(214/623),两组比较,差异有统计学意义(x2=63.404,22.320,25.384,P＜0.05).进一步根据UC临床症状进行分层分析,远端UC组和广泛UC组中GSTT1(-)、GSTP1(Val/Val)的分布频率分别为71.6%(164/229)、57.6%(132/229)和31.7%(13/41)、29.3%(12/41),两组比较,差异有统计学意义(x2=24.528,9.609,P＜0.05).远端UC组与广泛UC组的GSTM1(-)基因型的分布频率分别为65.1%(149/229)和56.1%(23/41),两组比较,差异无统计学意义(x2=1.210,P＞0.05).远端UC组和广泛UC组中GSTT1(-)和GSTP1(Val/Val)的分布频率分别为71.6%(164/229)、31.7%(13/41)和57.6%(132/229)、29.3%(12/41),两组比较,差异有统计学意义(x2=24.528,9.609,P＜0.05).轻中度UC组和重度UC组中GSTM1(-)、GSTT1(-)、GSTP1(Val/Val)分布频率比较,差异无统计学意义(x2=0.623,1.884,3.403,P＞0.05).结论 突变的GSTs基因型与湖北汉族人群的UC发生明显相关.GSTs突变基因型可能与UC患者病情严重程度无关.

Abstract：

Objective To investigate the correlation between genetic polymorphisms of glutathione S-transferases (GSTs) and ulcerative colitis (UC) in Hubei Han population. Methods Genetic polymorphisms of GSTM1 and GSTT1 of 270 patients with UC (UC group) who were admitted to the Zhongnan Hospital, People's Hospital of Wuhan University, Tongji Hospital and Union Hospital of Huazhong University of Science and Technology from August 2002 to December 2009 and 623 healthy people ( control group) were detected by restriction fragment length polymorphism-polymerase chain reaction. All UC patients were allocated to distal UC group (n= 229) and extensive UC group (n =41 ) according to the location of the lesions; and all UC patients were also allocated to mild-moderate group (n = 237) and severe group (n = 33 ). The genetic polymorphisms of GSTP1 of these patients and healthy people were detected by polymerase chain reaction. The genotypes of GSTM1, GSTT1 and GSTP1 were also detected. GSTM1 and GSTT1 containing small DNA segments ( 157 bp and 480 bp) were defined as GSTM1 (+) and GSTT1 (+), otherwise, GSTM(-) and GSTT1 (-), respectively. All data were analyzed by chisquare test. Results The frequencies of GSTM1(-), GSTT1(-) and GSTP1 (Val/Val) were 70.7% (191/270),64.8% (175/270) and 48.9% (132/270) in the UC group, and 41.7% (260/623), 47.2% ( 294/623 ) and 34.3% (214/623) in the control group, with a significant difference between the two groups (x2 = 63. 404,22. 320, 25. 384, P ＜0.05 ). The frequencies of GSTT1 (-) and GSTP1 (Val/Val) were 71.6% (164/229) and 57.6% (132/229) in the distal UC group, which were significantly higher than 31.7% (13/41) and 29.3%( 12/41 ) in the extensive UC group ( x2 = 24.528, 9.609, P ＜ 0.05 ). The frequencies of GSTM1 (-) were 65.1%(149/229) in the distal UC group and 56.1% (23/41) in the extensive UC group, with no significant difference between the two groups ( x2 = 1. 210, P ＞ 0.05 ). The frequencies of GSTT1 (-) and GSTP1 ( Val/Val ) were 71.6%(164/229), 31.7% ( 13/41 ) in the distal UC group and 57.6% ( 132/229), 29.3% ( 12/41 ) in the extensive UC group, with a significant difference between the two groups ( x2 = 24. 528, 9. 609, P ＜ 0. 05 ). There was no significant difference in the frequencies of GSTM1 (-), GSTT1 (-), GSTP1 (Val/Val) in the mild-moderate group and the severe group( x2 = 0. 623, 1. 884, 3. 403, P ＞ 0. 05 ). Conclusions Variant genotypes of GSTs are significantly correlated with UC in Hubei Han population. The severity of UC may not be correlated with variant genotypes of GSTs.     

谷胱甘肽转硫酶基因多态性与湖北汉族人群溃疡性结肠炎的关系

Objective To investigate the correlation between genetic polymorphisms of glutathione S-transferases (GSTs) and ulcerative colitis (UC) in Hubei Han population. Methods Genetic polymorphisms of GSTM1 and GSTT1 of 270 patients with UC (UC group) who were admitted to the Zhongnan Hospital, People's Hospital of Wuhan University, Tongji Hospital and Union Hospital of Huazhong University of Science and Technology from August 2002 to December 2009 and 623 healthy people ( control group) were detected by restriction fragment length polymorphism-polymerase chain reaction. All UC patients were allocated to distal UC group (n= 229) and extensive UC group (n =41 ) according to the location of the lesions; and all UC patients were also allocated to mild-moderate group (n = 237) and severe group (n = 33 ). The genetic polymorphisms of GSTP1 of these patients and healthy people were detected by polymerase chain reaction. The genotypes of GSTM1, GSTT1 and GSTP1 were also detected. GSTM1 and GSTT1 containing small DNA segments ( 157 bp and 480 bp) were defined as GSTM1 (+) and GSTT1 (+), otherwise, GSTM(-) and GSTT1 (-), respectively. All data were analyzed by chisquare test. Results The frequencies of GSTM1(-), GSTT1(-) and GSTP1 (Val/Val) were 70.7% (191/270),64.8% (175/270) and 48.9% (132/270) in the UC group, and 41.7% (260/623), 47.2% ( 294/623 ) and 34.3% (214/623) in the control group, with a significant difference between the two groups (x2 = 63. 404,22. 320, 25. 384, P ＜0.05 ). The frequencies of GSTT1 (-) and GSTP1 (Val/Val) were 71.6% (164/229) and 57.6% (132/229) in the distal UC group, which were significantly higher than 31.7% (13/41) and 29.3%( 12/41 ) in the extensive UC group ( x2 = 24.528, 9.609, P ＜ 0.05 ). The frequencies of GSTM1 (-) were 65.1%(149/229) in the distal UC group and 56.1% (23/41) in the extensive UC group, with no significant difference between the two groups ( x2 = 1. 210, P ＞ 0.05 ). The frequencies of GSTT1 (-) and GSTP1 ( Val/Val ) were 71.6%(164/229), 31.7% ( 13/41 ) in the distal UC group and 57.6% ( 132/229), 29.3% ( 12/41 ) in the extensive UC group, with a significant difference between the two groups ( x2 = 24. 528, 9. 609, P ＜ 0. 05 ). There was no significant difference in the frequencies of GSTM1 (-), GSTT1 (-), GSTP1 (Val/Val) in the mild-moderate group and the severe group( x2 = 0. 623, 1. 884, 3. 403, P ＞ 0. 05 ). Conclusions Variant genotypes of GSTs are significantly correlated with UC in Hubei Han population. The severity of UC may not be correlated with variant genotypes of GSTs.     

马兜铃酸肾病的临床与慢性化机制的研究进展

含马兜铃酸类成分中药导致的肾脏损害一马兜铃酸肾病近年受到国内外医药学界的广泛关注。该病临床表现复杂多样,主要病理特点呈快速进展性肾间质纤维化,常导致慢性进行性肾衰竭;并且在我国该病属常见病、多发病,危害甚广。本文从马兜铃酸肾病的临床特征、致肾间质纤维化机制等方面做一综述。     

马兜铃酸肾病的临床及发病机制研究概况

近年来,有关中草药肾毒性的报道逐年增多,其中马兜铃酸肾病成为中草药不良反应的典型受到了广泛关注.该病起病隐匿,进展较快,预后不良,治疗尚无成熟方案.本文从临床与病理、发病机制及疾病的防治等方面时马兜铃酸肾病进行了论述.重点介绍了该病发生发展过程中的关键细胞因子和生长因子重要作用的研究.     

马兜铃酸肾病的临床及发病机制研究概况

近年来,有关中草药肾毒性的报道逐年增多,其中马兜铃酸肾病成为中草药不良反应的典型受到了广泛关注.该病起病隐匿,进展较快,预后不良,治疗尚无成熟方案.本文从临床与病理、发病机制及疾病的防治等方面时马兜铃酸肾病进行了论述.重点介绍了该病发生发展过程中的关键细胞因子和生长因子重要作用的研究.     

Association of GSTT1, GSTM1 and GSTP1 gene polymorphism with aristolochic acid nephropathy

Objective To investigate the association of genetic polymorphisms in glutathione S-transferases T1 (GSTT1), M1 (GSTM1) and P1 (GSTP1) with aristolochic acid nephropathy (AAN) of Chinese people in Wenzhou of China. Methods Fifty-nine patients with AAN (AAN group) including 29 male and 30 female as well as 157 healthy ethnically matched controls (control group) including 93 male and 64 female were enrolled in this study. The genotypes of GSTT1, GSTM1 and GSTP1 were determined by multiple PCR and confronting two-pair primers PCR (CTPP-PCR). Results The genotype frequencies of GSTP1 were in Hardy-Weinberg equilibrium. Compared with the healthy controls, the frequency of GSTT1 null genotype was significantly higher in the patients with AAN (66.1％ vs 48.4％，P<0.05). Risk of AAN for individuals with GSTT1 null genotype was 1.747 fold of those without GSTTI null genotype (95% CI=0.818-3.731). The frequency of GSTM1 null genotype, GSTP1 variant genotypes and GSTP1 G allele in the patients and in the controls were 40.7％, 28.8％, 16.1％ and 47.8％, 31.8％, 17.5％, respectively, which were not significantly different. No significant differences were found in prevalence of GSTM1 and GSTP1 gene distribution between patients and controls. Conclusion GSTT1 gene polymorphism appears to be associated with susceptibility to AAN in Southern China.     

GSTP1, GSTM1, and GSTT1 genetic polymorphisms in patients with cryptogenic liver cirrhosis

We investigated glutathione S-transferase (GST) P1I le (105) Val, T1, and M1 polymorphisms in 45 patients with documented cryptogenic cirrhosis and 56 healthy control subjects. Polymerase chain reaction-based procedures were performed in the studied populations to confirm the genotypes of GSTT1, M1, and P1. Ile/Val and Val/Val GSTP1 genotypes were more frequent in the patients with cirrhosis (n = 39, 87%) than in the control subjects (n = 10; 18%) (odds ratio [OR] 34.04; 95% confidence interval [CI] 10.70 to 108.31, P < 0.001). Among these patients with cirrhosis, 16 were heterozygous and 23 were homozygous, whereas only one person in the control group was homozygous. The GSTM1 null genotype was also more prevalent in cirrhotic patients than in healthy control subjects (OR 6.83, 95% CI 2.53 to 18.42, P < 0.001). The rate of GSTT1 deletion did not show a significant difference between the two groups (OR 2.35, 95% CI 0.76 to 7.28, P = 0.111). To our knowledge, this is the first evidence that GSTP1 and GSTM1 polymorphisms may be related to the development of cirrhosis by unknown mechanisms. The significant association of cryptogenic cirrhosis with Val/Val GSTP1 genotype encoding a low detoxification activity protein implicates this polymorphism as a risk factor for the occurrence of the disease. Presented as an abstract at the Forty-Fourth Annual Meeting of The Society for Surgery of the Alimentary Tract, Orlando, Florida, May 19–22, 2003 (Poster of Distinction).     

Association between GSTM1, GSTT1, and GSTP1 variants and the risk of end stage renal disease

Introduction: There are some evidences indicating DNA damage by oxidant and mutant agents has an essential role in the chronic renal failure and end stage renal disease (ESRD). To investigate the possible association of GSTs variants with ESRD, we investigated the frequency of GST- T1, M1, and P1 genotypes, and the level of malondialdehyde (MDA) in patients with ESRD.

Materials and methods: The present case-control study consisted of 136 ESRD patients treated with maintenance hemodialysis and 137 gender- and age-matched, unrelated healthy controls from the population of west of Iran. The GST- T1, M1, and P1 genotypes were determined in all individuals using multiplex-PCR and PCR-RFLP. The level of MDA was measured by high-performance liquid chromatography (HPLC).

Results: We found that GSTM1 and GSTT1 null genotypes (GSTT1?/GSTM1?) increased the risk of ESRD by 1.8 times (p?<?0.001) and the increased risk of ESRD for GSTM-null (T1+-M1?) genotype was 3.04 times (p?=?0.002). ESRD patients carriers the GST (GSTM1-null?+?GSTT1-null?+?GST-null) genotypes compared to GST normal genotype increased the risk of ESRD by 3.3 (p?<?0.001) times. ESRD patients carriers of GST-null, GSTM1-null, and GSTT1-null genotypes had greater MDA concentration compared with the same genotypes of control subjects. Our results indicated that the GST-null allele (GSTT1-null/GSTM1-null) is a risk factor for ESRD and carriers of this allele have high levels of MDA.

Conclusion: Our findings indicate that oxidative stress, impairment of the antioxidant system and abnormal lipid metabolism may play a role in the pathogenesis and progression of ESRD and its related complications. These data suggest that patients with ESRD are more susceptible to vascular diseases.     

慢性马兜铃酸肾病患者伴发泌尿系统肿瘤

目的探讨慢性马兜铃酸肾病患者伴发泌尿系肿瘤情况。方法回顾分析102例慢性马兜铃酸肾病患者中4例伴发泌尿系肿瘤患者的临床资料。结果(1)4例患者均有长期间断小剂量服含马兜铃酸药物史,并被确诊为慢性马兜铃酸肾病,慢性肾功能不全;(2)4例均有明显血尿,相差显微镜检查呈均一红细胞尿,其中2例有肉眼血尿;(3)膀胱镜检查、逆行尿路造影及手术证实,3例为膀胱乳头状移行细胞癌,1例为肾盂移行细胞癌。结论慢性马兜铃酸肾病患者若出现明显均一红细胞血尿时,即应高度警惕泌尿系肿瘤发生。     

Association of polymorphisms in glutathione S-transferase genes (GSTM1, GSTT1, GSTP1) with idiopathic azoospermia or oligospermia in Sichuan,China

The reported effects of the glutathione S-transferase (GSTs) genes (GSTM1, GSTT1, and GSTP1) on male factor infertility have been inconsistent and even contradictory. Here, we conducted a case-control study to investigate the association between functionally important polymorphisms in GST genes and idiopathic male infertility. The study group consisted of 361 men with idiopathic azoospermia, 118 men with idiopathic oligospermia, and 234 age-matched healthy fertile male controls. Genomic DNA was extracted from the peripheral blood, and analyzed by polymerase chain reaction and restriction fragment length polymorphism analysis. There was a significant association between the GSTP1 variant genotype (Ile/Val + Val/Val) with idiopathic infertility risk (odds ratio [OR]: 1.53; 95% confidence interval [CI]: 1.11–2.11; P = 0.009). Similarly, a higher risk of infertility was noted in individuals carrying a genotype combination of GSTT1-null and GSTP1 (Ile/Val + Val/Val) (OR: 2.17; 95% CI: 1.43–3.31; P = 0.0002). These results suggest an increased risk of the GSTP1 variant genotype (Ile/Val + Val/Val) for developing male factor infertility. Our findings also underrate the significance of the effect of GSTM1 and/or GSTT1 (especially the former) in modulating the risk of male infertility in males from Sichuan, southwest China.     

Study on malignancy of end-stage aristolochic acid nephropathy patients in Wenzhou area

Objective To investigate the features of malignancy in end-stage aristolochic acid nephropathy (AAN) patients undergoing renal replacement therapy in the First Affiliated Hospital of Wenhou Medical University. Methods One hundred and two patients diagnosed as end-stage AAN during 2004 to 2013 were enrolled in the study, and separately udergoing hemodialysis, peritoneal dialysis and renal transplantation, to study the features of the malignancy and its risk factors. Results (1) There were totally 42 AAN patients suffering from malignancy, and 39 of them had urinary cancer. Eight cases of urinary cancer had metastasis, and 11 cases of bladder cancer had repeated recurrences. Patients suffering from malignancy had an increased mortality compared to patients without malignancy(13/42 vs 7/60, P=0.022). (2) Thirteenmalignacy cases were diagnosed before the end-stage of AAN, the rest cases appeared in 1-13 years[(4.62±3.31) years] after renal replacement. (3) A further logistic regression analysis of the 29 maligancy patients after renal replacement showed that, the dose of aristolochic acid (counted by Mutong) was the only risk factor of malignancy (P=0.091), compared with the dose of Mutong less than 60 g, the patients with an accumulated dose of Mutong more than 200 g had a 4.26 folds（95%CI 1.02, 17.83）higher risk of malignancy. There was no statistic difference of the malignancy risk among different renal replacement therapies, which however might influence the pathogenic sites of the urinary cancer. The simple bladder cancer was the most common malignancy among the hemodialysis patients (72.72%), and the upper urinary tract cancer among the peritoneal dialysis patients (66.67%), while the complex of both were dominant among the renal transplantation patients(40.00%). Conclusions Among the end-stage of AAN patients undergoing renal replacement therapy in Wenzhou area, the incidence of urinary cancer is high, with a character of complex, multiple and repeated recurrences. The occurence of malignancy seems to be separated from the renal function, but turns out obviously dose-dependent. There was no statisticaldifference of cancer risk among hemodialysis, peritoneal dialysis, and renal transplantation, which may induce different pathogenic sites of the urinary cancer.     

慢性马兜铃酸肾病患者肾小管上皮细胞转分化的研究

目的探讨慢性马兜铃酸肾病。肾小管上皮细胞转分化与肾间质纤维化的关系。方法以慢性马兜铃酸肾病患者的肾组织为标本,作常规Masson染色化病理检查;用天狼星红组织化学(组化)染色检查胶原Ⅰ、Ⅲ表达;用免疫组化染色检查角蛋白(CK)、α-平滑肌肌动蛋白(α-SMA)、波形蛋白(Vim)及转化生长因子-β1(TGF-β1)表达。对结果进行定量或半定量分析。结果 肾间质Masson染色纤维化面积及胶原Ⅰ、Ⅲ面积,与肾小管间质α-SMA及Vim阳性表达面积呈显著正相关(P<0.05),与肾小管CK阳性表达面积呈显著负相关(P<0.05);病变过程中健存肾小管TGF-β1表达明显增强。结论慢性马兜铃酸肾病患者的肾小管上皮细胞可转分化为肌成纤维细胞,参与肾间质纤维化,而这细胞转分化很可能与其自身高表达TGF-β1相关。     

慢性马兜铃酸肾病大鼠模型的早期贫血机制探讨

目的 探讨慢性马兜铃酸肾病(CAAN)大鼠模型的早期贫血机制。方法 将78只Wistar雌性大鼠随机分为3组:(1)关木通组(n=30):予关木通水煎剂灌胃连续用药8周；(2)正常对照组(n=24):予饮用水灌胃，连续用药8周；(3)5/6肾切除组(n=24):自由饮水。在第8、12、16周分别随机处死各组大鼠总数的1/3，留取尿、血和骨髓组织标本，分别作生化、ELISA、HE染色、免疫组化、电镜、红细胞生成素(EPO)定量等检查。结果 关木通组大鼠和5/6肾切除组大鼠BUN和Scr从第8周开始升高，但关木通组大鼠肾功能损伤进展迅速。关木通组大鼠第12周开始出现贫血，第16周贫血加重，与正常对照组和5/6肾切除组相比，P < 0.01。关木通组大鼠早期血清和骨髓组织TNF-α和IL-1β表达明显增多，与正常对照组和5/6肾切除组相比，P<0.01。随着病情进展血窦内皮损伤加重，骨髓组织CD34表达、微血管密度MVD和造血组织面积逐渐下降，与正常对照组和5/6肾切除组相比差异有统计学意义，P < 0.01。各组大鼠血清EPO定量比较，差异没有统计学意义。 结论 CAAN大鼠模型血清和骨髓组织早期TNF-α和IL-1β表达明显增多，骨髓微血管损伤可能是其贫血发生早且较严重的原因。     

慢性马兜铃酸肾病大鼠贫血发生的机制

目的 探讨慢性马兜铃酸肾病（CAAN）贫血的发生机制。 方法 用62只SD大鼠筛查血红蛋白（Hb）,求正常值。随机选择24只Hb正常的大鼠,分为对照组及模型组,各12只,后者予关木通浸膏水溶液间断灌胃制作CAAN模型。在给药前及8周末,分别检测两组各6只大鼠体质量、Hb、尿蛋白量（24 h）及肌酐清除率（Ccr）,然后处死大鼠,留取肾组织做Masson染色观察肾间质纤维化程度;实时定量PCR法检测肾组织中红细胞生成素（EPO）mRNA表达;免疫组化染色观察肾组织中Ⅰ型胶原（ColⅠ）、氨基肽酶P（APP）、低氧诱导因子（HIF）1α及2α的蛋白表达。 结果 大鼠的正常Hb值为（155.9±16.5） g/L,低于123.6 g/L为贫血。给药前,对照组与模型组间各指标的差异均无统计学意义。8周末时,与对照组比较,模型组大鼠Hb和Ccr显著下降[（121.66±15.68） g/L比（169.00±12.89） g/L,（0.63±0.13） ml/min比（1.27±0.18） ml/min];尿蛋白量（24 h）显著增多[（27.04±9.40） mg/d比（6.11±0.84） mg/d];肾间质纤维化相对面积及ColⅠ相对面积显著增加[（12.89±2.33）%比（0.55±0.10）%,（13.92±2.92）%比（1.32±0.84）%];肾组织APP蛋白表达和EPO mRNA表达显著下调 [（0.55±0.23）%比（3.77±1.06）%,0.005±0.001比0.032±0.013];HIF-1α和HIF-2α蛋白表达显著上调 （2.55±0.16比1.12±0.46,2.33±0.33比1.15±0.27）（均P < 0.01）。 结论 CAAN的贫血发生可能与肾小管周毛细血管毁坏所导致的EPO产生减少有关,虽然HIF表达已代偿性增强,但仍未能阻止贫血发生。