Empirical Assessment of Bacillus Calmette-Guérin Vaccine to Combat COVID-19

COVID-19 has become one of the critical health issues globally,which surfaced first in latter part of the year 2019.It is the topmost concern for many nations’governments as the contagious virus started mushrooming over adjacent regions of infected areas.In 1980,a vaccine called Bacillus Calmette-Guérin(BCG)was introduced for preventing tuberculosis and lung cancer.Countries that have made the BCG vaccine mandatory have witnessed a lesser COVID-19 fatality rate than the countries that have not made it compulsory.This paper’s initial research shows that the countries with a longtermcompulsory BCGvaccination system are less affected by COVID-19 than those without a BCG vaccination system.This paper discusses analytical data patterns for medical applications regarding COVID-19 impact on countries with mandatory BCG status on fatality rates.The paper has tackled numerous analytical challenges to realize the full potential of heterogeneous data.An analogy is drawn to demonstrate how other factors can affect fatality and infection rates other than BCG vaccination only,such as age groups affected,other diseases,and stringency index.The data of Spain,Portugal,and Germany have been taken for a case study of BCG impact analysis.

Intravesical bacillus Calmette-Guerin(BCG)in treating non-muscle invasive bladder cancer—analysis of adverse effects and effectiveness of two strains of BCG(Danish 1331 and Moscow-I)

Objective:To compare the differences in adverse effects and efficacy profile between bacillus Calmette-Guerin(BCG)Danish 1331 and BCG Moscow-I strain in management of non-muscle invasive bladder cancer.Methods:Clinical data of 188 cases of non-muscle invasive bladder cancer treated with BCG between January 2008 and December 2018 in our institute were collected prospectively and analysed retrospectively,and 114 patients who completed a minimum of 12 months of follow-up were analysed.Patient and tumor characteristics,strain of BCG,adverse effects,and tumor progression were included for analysis.Intravesical BCG was instilled in intermediate-and high-risk patients.Six weeks of induction BCG,followed by three weekly maintenance BCG at 3,6,12,18,and 24 months was advised in high-risk patients.Results:Overall 68 patients received BCG Danish 1331 strain and 46 patients received Moscow-I strain.Patient and tumor characteristics were well balanced between the two groups.The median follow-up period was 42.5 months and 34.5 months in Danish 1331 and Moscow-I groups,respectively.Adverse events like dropout rate,antitubercular treatment requirement,and need of cystectomy were higher in Moscow-I group(n=31,67.4%)when compared to Danish 1331 strain(n=33,48.5%)(p=0.046).On direct comparison between Danish 1331 and Moscow-I strain,there was similar 3-year recurrence-free survival(80.0%vs.72.9%)and 3-year progression-free survival(96.5%vs.97.8%).Conclusion:Study results suggest no significant differences between Danish 1331 and Moscow-I strain in recurrence-free survival and progression-free survival,but a significantly higher incidence of moderate to severe adverse events in BCG Moscow-I strain.

Multi-organ failure with atypical liver granulomas following intravesical Bacillus Calmette-Guerin instillation

Bacillus Calmette-Guerin(BCG) intravesical instillation has been adopted in the treatment of patients with superficial bladder cancer.BCG-induced disseminated infection,though rare,has been associated with the histological finding of epithelioid granulomas in different organs,including the liver.We report the case of an adult patient with multi-organ failure,who developed sepsis,acute respiratory failure and acute hepatic failure with encephalopathy whose liver biopsy confirmed the presence of atypical,granulomatous-like lesions.Recovery was observed only after empirical therapy for Mycobacterium bovis with isoniazid,rifampicin,ethambutol and steroids was introduced.This case highlights the importance of a thorough patient assessment in order to exclude other more common causes of hepatic granulomas and to confirm diagnosis.Histological findings may be non-specific when the liver is involved in BCGinduced disseminated infection.

The natural course of bacillus Calmette-Guerin induced bladder lesions:A long-term follow-up study and systematic review

Objective:Bacillus Calmette-Gue´rin(BCG)instillation is the standard adjuvant treatment for intermediate-and high-risk non-muscle-invasive bladder cancer after transurethral resection.Nevertheless,its toxicity often causes bladder complications.On follow-up cystoscopy,post-BCG bladder lesions can be pathologically benign,urothelial carcinoma recurrence,or other types of bladder malignancy.Only a small number of case reports have been published on post-BCG bladder lesions.Their clinical features,natural course,and management remain unknown.Methods:We retrospectively studied cystoscopic videos and medical records of BCG-treated bladder cancer patients at our center.During a long-term follow-up,we took biopsies on tumor-like lesions and described their changes.In addition,we summarized previous studies on post-BCG bladder lesions by systematic literature searching and review.Results:We described a series of three cases with post-BCG bladder lesions mimicking tumor recurrence from a total of 38 cases with follow-up data for more than 5 years.Those lesions could last,grow,or disappear spontaneously,and remain pathological benign for years.In systematic review,we identified and analyzed a total of 15 cases with post-BCG bladder lesions with detailed clinical information.Eleven of the 15 were benign and have a good prognosis with nephrogenic adenoma being the most common pathological type.Conclusion:Based on previous studies and our experience,benign lesions after BCG instillation cannot distinguish with cancer recurrence by cystoscopy alone,even under narrow band imaging mode.Nonetheless,given most of them have a good prognosis,random biopsy or transurethral resection might be spared in the patients with long-term negative biopsy and urine cytology.

An efficient fusion protein system for expression of Bacillus anthracis protective antigen as immunogenic and diagnostic antigen

Objective:To produce high quantities of recombinant protective antigen(rPA) for human vaccine and diagnosis.Methods:The PA gene was amplified by PCR with pXO1 plasmid as template. The PCR product was cloned into pMAL-c2X vector using the BamH1 and SalI restriction enzymes.The recombinant plasmid was transformed into Escherichia coli DH5 a strain and then screened for transformation.The expression of protective antigen was analyzed by SDS-PAGE and Western blotting after isopropyl β-D-thiogalactopyranoside(IPTG) induction.Results: The full-length PA gene(2.2 kb) was cloned into pMAL vector system.The recombinant vector was confirmed by restriction enzyme and PCR analysis.The expression of cytoplasmic maltose-binding protein-protective(MBP-P) antigen fusion protein was detected by SDS-PAGE and Western blotting,and obtained a 125 kDa protein band,which was similar to expected size of fusion protein.Conclusions:This expression system can be used in the high production of rPA. After purification and immunization studies,the purified rPA may be used in the development of the human recombinant anthrax vaccine and also in diagnosis of anthrax disease.

Candidate Vaccines against Tuberculosis and the Future of Novel TB Vaccine Research

Introduction: Tuberculosis (TB) continues to be a global health challenge and currently only one licensed vaccine is available. For nearly 100 years, the Bacillus Calmette-Guérin (BCG) vaccine has been in use. While it provides protection against disseminated TB in infants, its protection against adult and adolescent pulmonary tuberculosis (PTB) is variable. This literature review will provide an overview of the clinical status of candidate TB vaccines and discuss the challenges and future development trends of novel TB vaccine research, in combination with a general overview of the Tuberculosis (TB) disease and Mycobacterium tuberculosis itself. Methods: Bibliographic searches were carried out on medical journal databases, publishers, and aggregators. The most used databases were PubMed, NCBI and MDPI. Publications in English on these and other databases relating to novel TB vaccines were included in this review. Results: Currently, there are 12 main vaccine candidates in various phases of clinical trials, they include four protein or adjuvant vaccines, three viral-vectored vaccines, three mycobacterial whole cells or extract vaccines, and one each of the recombinant life and the attenuated Mycobacterium tuberculosis vaccine. Currently, the most likely candidate vaccines are the M72 + AS01E and Vaccae vaccines. M72 + AS01E is a recombinant fusion protein vaccine candidate, clinical trials showed that administering two doses of M72/AS01E was successful in reducing the development of active TB disease with 50% efficacy. Studies have also proven the efficacy of Vaccae (which is currently in phase III clinical trials) as an adjunctive therapy, with it being curative in conjunction with current therapy. Conclusion: Given the morbidity and mortality suffered globally by M. tuberculosis, it is time to realize the seriousness of the situation and accelerate our commitment and investment to the eradication of this infectious disease. With the number of vaccine candidates currently in clinical trials having promising results, it is imperative to continue these studies and accelerate towards phase III licensure trials if we are to achieve the milestone of “End TB Strategy” by 2035. Today, we are witnessing immense progress in both preclinical and clinical TB vaccine research despite disappointing results from some of the clinical efficacy trials like that of MVA85A. We can revisit the design of vaccines and learn from them. It is important not only to recognize and give credit to those that have tested well in human trials, such as M72 + AS01E, but to expedite and improve its efficacy through funding of its research.

BYL-719对结核杆菌诱导异常破骨细胞分化的作用及机制

背景:PI3K/AKT信号通路调控破骨激活在维持骨稳态中具有关键作用,而骨关节结核中的骨质破坏正是由于结核杆菌感染引起的异常破骨细胞生成所致,但是PI3K信号通路在结核杆菌诱导的异常破骨细胞生成中发挥的作用尚不明确。目的:探究PI3K/AKT信号通路抑制剂BYL-719对结核杆菌诱导的异常破骨细胞生成的影响及机制。方法:使用牛结核杆菌卡介苗(BCG)感染RAW264.7细胞,Ag85B进行细胞免疫荧光染色;CCK-8法确定BYL-719安全使用浓度。实验分为空白对照组、BYL-719组、卡介苗组、卡介苗+BYL-719组。各组细胞在RANKL诱导下,通过抗酒石酸酸性磷酸酶染色和鬼笔环肽染色,探究BYL-719对结核杆菌感染后破骨细胞分化、融合的影响;RT-PCR和Western Blot检测破骨细胞相关基因及蛋白表达情况,并进一步探索作用机制。结果与结论:①免疫荧光染色结果显示,RAW264.7细胞吞噬结核杆菌;②CCK-8数据显示,40 nmol/L浓度BYL-719没有细胞毒性;③抗酒石酸酸性磷酸酶染色和鬼笔环肽染色提示,BYL-719能抑制结核杆菌感染后的破骨细胞生成、融合能力;④RT-PCR和Western blot结果也提示,BYL-719抑制了结核杆菌感染诱导的破骨细胞特异性基因(包括c-Fos、NFATc1、基质金属蛋白酶9和CtsK)表达升高(P<0.05);⑤Western blot和免疫荧光染色结果揭示,BYL-719通过下调IκBα-p65来抑制结核杆菌诱导的破骨细胞过度分化;⑥结论:BYL-719通过下调IκBα/p65抑制结核杆菌诱导的异常破骨细胞生成,说明IκBα/p65信号通路是骨关节结核潜在治疗靶点,BYL-719有预防和改善骨关节结核中骨质破坏的潜在价值。

Antitumor effects of human interferon-alpha 2b secreted by recombinant bacillus Calmette-Guérin vaccine on bladder cancer cells

Objective:Our objective was to construct a recombinant bacillus Calmette-Guérin vaccine(rBCG) that secretes human interferon-alpha 2b(IFNα-2b) and to study its immunogenicity and in vitro antitumor activity against human bladder cancer cell lines T24 and T5637.Methods:The signal sequence BCG Ag85B and the gene IFNα-2b were amplified from the genome of BCG and human peripheral blood,respectively,by polymerase chain reaction(PCR).The two genes were cloned in Escherichia coli-BCG shuttle-vector pMV261 to obtain a new recombinant plasmid pMV261-Ag85B-IFNα-2b.BCG was transformed with the recombinant plasmid by electroporation and designated rBCG-IFNα-2b.Mononuclear cells were isolated from human peripheral blood(PBMCs) and stimulated with rBCG-IFNα-2b or wild type BCG for 3 d,and then cultured with human bladder cancer cell lines T24 and T5637.Their cytotoxicities were measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT) assay.Results:BCG was successfully transformed with the recombinant plasmid pMV261-Ag85B-IFNα-2b by electroporation and the recombinant BCG(rBCG-IFNα-2b) was capable of synthesizing and secreting cytokine IFNα-2b.PBMC proliferation was enhanced significantly by rBCG-IFNα-2b,and the cytotoxicity of PBMCs stimulated by rBCG-IFNα-2b to T24 and T5627 was significantly stronger in comparison to wild type BCG.Conclusions:A recombinant BCG,secreting human IFNα-2b(rBCG-IFNα-2b),was constructed successfully and was superior to control wild type BCG in inducing immune responses and enhancing cytotoxicity to human bladder cancer cell lines T24 and T5637.This suggests that rBCG-IFNα-2b could be a promising agent for bladder cancer patients in terms of possible reductions in both clinical dosage and side effects of BCG immunotherapy.

Proteomics Reveals that Proteins Expressed During the Early Stage of Bacillus anthracis Infection Are Potential Targets for the Development of Vaccines and Drugs

In this review, we advance a new concept in developing vaccines and/or drugs to target speci?c proteins expressed during the early stage of Bacillus anthracis (an- thrax) infection and address existing challenges to this concept. Three proteins (immune inhibitor A, GPR-like spore protease, and alanine racemase) initially identi?ed by proteomics in our laboratory were found to have di?erential expres- sions during anthrax spore germination and early outgrowth. Other studies of di?erent bacillus strains indicate that these three proteins are involved in either germination or cytotoxicity of spores, suggesting that they may serve as potential targets for the design of anti-anthrax vaccines and drugs.

枯草芽孢杆菌的生理功能及其在畜禽生产中的应用

枯草芽孢杆菌是一类可形成芽孢的具有多种生理功能且对动物机体无毒副作用的理想益生菌。在饲料中添加枯草芽孢杆菌具有调节畜禽肠道功能、平衡微生物区系,提高免疫力和促生长等作用。枯草芽孢杆菌还可以作为饲料发酵菌种,经发酵后的饲料会降低抗营养因子的含量,提高营养物质的含量,从而促进畜禽对饲料养分的消化和吸收。枯草芽孢杆菌内生芽孢的特性,可以保证其在饲料生产和畜禽内环境条件下的功能稳定性以及作为疫苗表达载体的独特优势。因此,枯草芽孢杆菌在畜禽生产中具有十分广阔的应用前景。作者综述了枯草芽孢杆菌的生物学特性、生理功能及其在畜禽生产中的应用,以期为枯草芽孢杆菌在畜禽生产中的应用提供一定的参考。

The Regulatory Effects of Polyporus Polysaccharide on the Nuclear Factor Kappa B Signal Pathway of Bladder Cancer Cells Stimulated by Bacillus Calmette-Guerin

Objective：To detect the effects of Polyporus polysaccharide（PPS）,Bacillus Calmette-Guerin （BCG）,and their combination on the nuclear factor kappa B（NF-κB）signaling pathway associated-gene expression and investigate the molecular mechanisms of the toxic-reducing effect of PPS in coordination with BCG against bladder cancer.Methods：After T739 cells were treated with PPS,BCG and their combination, the changes in mRNA and protein expression of inhibitor of kappa B kinase beta（IKKβ）,NF-κB subunit p65 （NF-κB p65）,intracellular adhesion molecule 1（ICAM1）and chemokine（C-c motif）ligand 2（CCL2）in bladder cancer cell line T739 were determined by relative quantitative real-time PCR,Western blot,and flow cytometry （FCM）.NF-κB p65 DNA-binding activity in T739 cell was detected by biotinylated probe-ELISA,and NF-κB p65 nuclear expression in T739 cell was observed by immunohistochemistry.Results：Compared with the T739 control group,the mRNA expression of IKBKB（IKKβ）,Rel A（NF-κB p65）,ICAM1 and CCL2 in T739 cells treated with BCG were increased obviously（Ratio2.0）,as well as the expression of IKKβ,CCL2 and ICAM1 proteins.Meanwhile,NF-κB p65 DNA-binding activity and NF-κB p65 nuclear expression in T739 cells treated with BCG were up-regulated significantly（P0.05）.Compared with the control,the increased expression in T739 cells were simultaneously down-regulated after PPS treatment,except for ICAM1 protein expression.With cells treated with a combination of BCG and PPS,the expression of genes associated with the NF-κB signaling pathway,such as IKBKB,ICAM1 and CCL2,were all down-regulated compared to the BCG group,as well as Rel A mRNA expression,NF-κB p65 DNA-binding activity and NF-κB p65 nuclear expression.Conclusions： PPS could inhibit the over-activation of the NF-κB signaling pathway induced by BCG in bladder cancer cells and accordingly attenuate the adverse reactions to BCG therapy.

Can intravesical bacillus Calmette-Guerin reduce recurrence in patients with non-muscle invasive bladder cancer？ An update and cumulative meta-analysis

Approximately 70% of newly diagnosed bladder tumors are non-muscle invasive bladder cancer （NMIBC）. NMIBC accounts for approximately 80% of total bladder cancer cases. Bacillus Calmette-Guerin （BCG） instillation and maintenance is considered as the standard adjuvant treatment for superficial bladder cancer. A number of randomized studies have focused on the benefit of maintenance therapy following initial BCG induction. To provide further insights into the effect of intravesical instillation on recurrence in patients with NMIBC, we analyzed this relationship by conducting an updated detailed meta-analysis. Evidence suggested that adjuvant intravesical BCG with maintenance treatment is significantly effective for the prophylaxis of tumor recurrence in patients with NMIBC.

Nano-Bacillus Calmette-Guérin immunotherapies for improved bladder cancer treatment

Cancer immunotherapy has rapidly become the fourth mainstream treatment alternative after surgery,radiotherapy,and chemotherapy,with some promising results.It aims to kill tumor cells by mobilizing or stimulating cytotoxic immune cells.However,the clinical applications of tumor immunotherapies are limited owing to a lack of adequate delivery pathways and high toxicity.Recently,nanomaterials and genetic engineering have shown great potential in overcoming these limitations by protecting the delivery of antigens,activating targeted T cells,modulating the immunosuppressive tumor microenvironment,and improving the treatment efficacy.bacillus Calmette-Gué;rin(BCG)is a live attenuated Mycobacterium bovis vaccine used to prevent tuberculosis,which was first reported to have antitumor activity in 1927.BCG therapy can activate the immune system by inducing various cytokines and chemokines,and its specific immune and inflammatory responses exert antitumor effects.BCG was first used during the 1970s as an intravesical treatment agent for bladder cancer,which effectively improved immune antitumor activity and prevented tumor recurrence.More recently,nano-BCG and genetically engineered BCG have been proposed as treatment alternatives for bladder cancer due to their ability to induce stronger and more stable immune responses.In this study,we outline the development of nano-BCG and genetically engineered BCG for bladder cancer immunotherapy and review their potential and associated challenges.

Protection of Citrullus colocynthis Fruit Extracts on Carbon Tetrachloride-induced and Bacillus Calmette-Guerin plus Lipopolysaccharide-induced Hepatotoxicity in Mice

Objective To investigate the hepatoprotective activities of the extracts from Citrullus colocynthis(ECC),a native plant used as traditional Uigur Medicine on acute liver injury in mice.Methods The activities of ECC of petroleum ether(ECCPE),chloroform(ECCC),ethyl acetate(ECCEA),n-butyl alcohol(ECCBA),and water(ECCW) were evaluated in vivo using two experimental models,carbon tetrachloride(CCl4)- and bacillus calmette-guerin(BCG) plus lipopolysaccharide(LPS)-induced acute hepatotoxicity in mice.The contents of aspartate aminotransferase(AST) and alanine aminotransferase(ALT) in serum were determined and the liver histological examination was carried out,respectively.Results The pretreatment with ECC for 7 d obviously reduced the impact of CCl4toxicity on the serum markers of liver damage,ECCEA and ECCC with a significant difference of AST(P < 0.01,0.05,respectively) and ALT(P < 0.05,0.01,respectively).The protective activity was reconfirmed against BCG + LPS-induced injury and the serum enzymatic levels were obviously elevated,for ECCEA and ECCC with a significant difference of AST(P < 0.05,0.01,respectively) and ALT(P < 0.01,0.05,respectively).Conclusion That ECCEA and ECCC are the potent hepatoprotective extracts that could protect liver against the acute injury,and this ability might be attributed to their hepatoprotective potentials.

播散性卡介菌病1例

卡介苗是一种预防结核病的减毒活疫苗,健康新生儿出生时即予以接种。轻度不良反应为接种2~3 d后,接种部位皮肤发红,触之无硬结,数日后自行消退。播散性卡介菌病是最严重的不良反应,临床表现主要为接种部位红肿、破溃和溢脓,全身多发性淋巴结肿大、皮肤包块形成和肺部病变,也可累及肝脏、脾脏和骨骼。该病致死率高,早期诊断及治疗方法的选择仍是难题。现就我科诊治的1例临床诊断的播散性卡介菌病诊治过程及相关文献复习总结如下,以期为相应专业的临床医师提供一定帮助。

Effects of Bacillus Calmette-Guerin on immunometabolism,microbiome and liver diseases

Metabolic diseases have overtaken infectious diseases as the most serious public health issue and economic burden in most countries.Moreover,metabolic diseases increase the risk of having infectious diseases.The treatment of metabolic disease may require a long-term strategy of taking multiple medications,which can be costly and have side effects.Attempts to expand the therapeutic use of vaccination to prevent or treat metabolic diseases have attracted significant interest.A growing body of evidence indicates that Bacillus Calmette-Guerin(BCG)offers protection against non-infectious diseases.The non-specific effects of BCG occur likely due to the induction of trained immunity.In this regard,understanding how BCG influences the development of chronic metabolic health including liver diseases would be important.This review focuses on research on BCG,the constellation of disorders associated with metabolic health issues including liver diseases and diabetes as well as how BCG affects the gut microbiome,immunity,and metabolism.

microRNA与结核病相互关系的研究进展

microRNA(miRNA)是一类广泛存在于各种生物体内的小分子非编码单链RNA,主要在转录后水平调控靶基因的表达。越来越多的证据表明它在细胞分化与沟通、机体发育、免疫反应等诸多方面都发挥着重要作用。尤其在疾病相关研究中,miRNA更是具有广泛的用途和美好的前景。本文主要针对miRNA的相关特性、与结核病(tuberculosis,TB)相互关系的研究进展以及应用前景等做综述。

新生期卡介苗和乙肝疫苗联合接种对哮喘小鼠IFN-γ、IL-4和IL-17A表达的影响

目的:观察新生期卡介苗(BCG)和乙肝疫苗(HepB)联合接种对哮喘小鼠干扰素γ(IFN-γ)、白细胞介素4(IL-4)和白细胞介素17A(IL-17A)表达的影响,探讨BCG和HepB联合接种对气道炎症的影响及可能机制。方法:BALB/c小鼠随机分为BCG和HepB联合接种造模[卵清蛋白(OVA)所致哮喘模型]组(B/H/O组)、BCG接种造模组(B/O组)、HepB接种造模组(H/O组)、BCG和HepB联合接种组(B/H组)、造模组(OVA组)、BCG组、HepB组和生理盐水对照(NS)组,每组6只。B/H/O组和B/H组于第0、7和14天分3次皮下注射1×105CFU的BCG,同时第0和28天分2次下肢腿部肌肉注射HepB 1.5μg,其它组单独接种BCG或HepB。OVA致敏和雾化吸入激发建立哮喘模型;末次激发24 h后取肺组织HE染色;收集支气管肺泡灌洗液(BALF)进行细胞总数计数和嗜酸性粒细胞(EOS)计数;ELISA法检测血清IFN-γ和IL-4及肺组织匀浆IL-17A的水平。结果:肺组织病理观察发现,OVA组、B/O组、B/H/O组和H/O组支气管周围大量炎症细胞浸润,气道上皮细胞增生肥大,B/H/O组和H/O组的炎症程度较OVA组重,B/O组则较OVA组轻。B/H/O组、B/O组和H/O组BALF细胞总数与OVA组比较均下降(P<0.05);EOS计数在B/H/O组比B/H组上升(P<0.05),B/O组比BCG组上升(P<0.05),H/O组比HepB组上升(P<0.05)。分别与H/O组、OVA组和NS组比较,HepB组的血清IFN-γ/IL-4比值均升高(P<0.05);分别与B/H/O组、B/O组、OVA组和NS组比较,B/H组的血清IFN-γ/IL-4比值均升高(P<0.05)。与OVA组比较,B/H/O组和B/O组的肺组织匀浆IL-17A水平均下降(P<0.05);与B/O组比较,B/H/O组的肺组织匀浆IL-17A水平进一步下降(P<0.05)。结论:卡介苗和乙肝疫苗联合接种有助于减轻哮喘模型小鼠肺部的炎症反应,其机制可能与降低IL-4分泌、提高IFN-γ/IL-4水平和抑制IL-17A的表达有关。

福建叶下珠抗小鼠免疫性肝损伤的实验研究

目的评价福建叶下珠对小鼠免疫性肝损伤的保护作用。方法48只NIH小鼠随机分为叶下珠高、低剂量组、联苯双酯组、正常对照组及模型组。于造模之日起,叶下珠高、低剂量组分别以20 g/kg、10 g/kg叶下珠药液灌胃,联苯双酯组以0.15 g/kg联苯双酯药液灌胃,正常对照组及模型组每天给予等量生理盐水。每天灌胃1次,连用12 d。检测血清谷丙转氨酶(ALT)和肝、脾脏器指数,并做肝脏病理学检查。结果联苯双酯组、叶下珠高、低剂量组小鼠血清ALT、肝指数、脾指数值较模型组有不同程度的改善(P<0.05,P<0.01)。炎症坏死程度:5组间比较,差异有非常显著性意义(P<0.005);模型组与正常组、联苯双酯组、福建叶下珠高、低剂量组与模型组间两两比较,差异有显著性意义(P值均<0.05);联苯双酯组与福建叶下珠大、小剂量组间比较,差异无显著性意义(P>0.05)。结论福建叶下珠能显著降低血清转氨酶活力和肝脾脏器指数,对肝细胞坏死有一定的改善作用,具有较好的抗小鼠免疫性肝损伤作用。