Chinese Journal of Animal Nutrition >

2026 , Vol. 38 >Issue 1: 36 - 47

DOI: https://doi.org/10.12418/CJAN2026.003

REVIEW

Research Progress on Effect of Four Kinds of Genuine Medicinal Materials in Hubei on Diarrhea of Weaned Piglets

  • WAN Fangyan , 1 ,
  • WANG Zifan 1 ,
  • MEI Zhinan 2 ,
  • SONG Tongxing , 1, *
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  • 1 College of Animal Science and Technology, Huazhong Agricultural University, Wuhan 430070, China
  • 2 College of Plant Science & Technology, Huazhong Agricultural University, Wuhan 430070, China
* associate professor, E-mail:

Received date: 2025-06-25

  Online published: 2026-01-13

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Abstract

The intestinal development of weaned piglets is incomplete, the function is not perfect, and the diarrhea symptoms are easy to occur, which affects the growth performance of piglets. Traditional Chinese veterinary medicine believe that piglets are weak in spleen and stomach, and are susceptible to cold, dampness and heat, resulting in spleen dysfunction, abnormal transmission of large and small intestine, and diarrhea. The traditional Chinese medicine (TCM) syndrome differentiation of diarrhea includes damp-heat accumulation, cold-dampness obstructing spleen, spleen qi deficiency and spleen deficiency and dampness. For different types, targeted prescriptions should be selected for syndrome differentiation and treatment. As the genuine medicinal materials in Hubei, the ten Chu medicines have the characteristics of excellent quality, large scale and good curative effect. Among them, Coptidis Rhizoma, Poria cocos, Atractylodis Rhizoma and Magnoliae Officinalis Cortex, as the representative drugs of the ten Chu medicines, have the effects of clearing heat and drying dampness, dispelling wind and dispelling cold, invigorating spleen and transporting dampness, and have a significant effect on improving piglet diarrhea. This paper systematically expounded the control effect and mechanism of four kinds of genuine medicinal materials in Hubei-Coptidis Rhizoma, Poria cocos, Atractylodis Rhizoma and Magnoliae Officinalis Cortex, on piglet’s diarrhea, as well as the application forms in actual production, so as to provide reference for the application of Hubei authentic medicinal materials in animal husbandry production.

Key words： genuine medicinal materials in Hubei; weaned piglets; diarrhea; gut microbiota

Cite this article

WAN Fangyan , WANG Zifan , MEI Zhinan , SONG Tongxing . Research Progress on Effect of Four Kinds of Genuine Medicinal Materials in Hubei on Diarrhea of Weaned Piglets[J]. Chinese Journal of Animal Nutrition, 2026 , 38(1) : 36 -47 . DOI: 10.12418/CJAN2026.003

断奶仔猪的肠道发育不完全、免疫能力较弱,易出现腹泻症状,造成生长发育缓慢甚至死亡[1]。中兽医典籍《元亨疗马集》指出,夫泄泻者,皆因脾胃虚弱,饮食不节,或寒温不适,以致清浊不分,水谷并下[2]。中医认为腹泻的根本在于脾胃功能失职,强调湿、寒、热邪侵袭肠道是诱因。因此,中医以辨证施治为原则,针对寒热错杂、脾虚湿盛、脾肾阳虚等不同分型使用不同功效的中药进行调理,恢复脾胃功能,达到止泻的目的[3]。
湖北省作为中药资源大省,中药材植物资源达4 457种,形成了五大中药材优势产区,已有全国知名道地药材16种,优势特色药材30种,是众多大宗药材的道地产区之一[4]。道地药材区别于其他中药材,具有特定产区且品质和疗效优于其他地区同种药材,因此获“道地”之名[5]。2022年7月,湖北省发布了“十大楚药”道地药材的评选结果,蕲艾、半夏、天麻、黄连、茯苓、福白菊、苍术、龟鳖甲、银杏、紫油厚朴和黄精(并列第10位)等11种药材上榜[4]。其中,黄连、茯苓、苍术和厚朴作为湖北道地药材,具有燥湿健脾、行气化湿的功效,在治疗泄泻方面具有显著疗效。本文将重点介绍湖北4种道地药材黄连、茯苓、苍术、厚朴对仔猪腹泻的治疗效果和作用机制,讨论其在实际生产中的应用方式,以期为后续的研究与应用提供参考。

1 湖北4种道地药材防治断奶仔猪腹泻的效果评价

中兽医认为仔猪出生后脾胃虚弱,湿浊不化,加之湿邪外侵,导致运化失常,清浊相干,引起泄泻[6]。黄连、茯苓、苍术和厚朴在防治仔猪腹泻方面都有显著效果,并且使用效果与抗生素相当。黄连具有清热燥湿、泻火解毒等功效,化学成分包括生物碱、多糖、黄酮等多种类型,活性成分以生物碱类的小檗碱为主[7]。研究发现,断奶仔猪饲粮中添加40和80 mg/kg小檗碱均可以显著降低腹泻率,并且40和80 mg/kg小檗碱的抗腹泻效果与2 000 mg/kg氧化锌(ZnO)近似[8]。茯苓具有利水渗湿、健脾宁心等功效,化学成分包括三萜和多糖等多种类型,茯苓的抗炎作用主要与多糖类成分有关[9]。陈丽玲等[10]发现,在断奶仔猪饲粮中添加白术茯苓多糖复方可以显著降低腹泻率,并且添加比例为0.06%时腹泻率可降至抗生素组(添加硫酸黏杆菌素20 mg/kg+杆菌肽锌40 mg/kg+喹乙醇100 mg/kg)水平。苍术具有燥湿健脾、祛风散寒等功效,化学成分包括倍半萜、烯炔、多糖和有机酸等多种类型,其中苍术酮是其发挥抗炎作用的主要有效成分[11-12]。陈博等[13]发现,在断奶仔猪基础饲粮中添加苍术提取物可以显著降低仔猪的腹泻指数。厚朴具有燥湿消痰、下气除满的功效,化学成分包括酚类、生物碱、挥发油和多糖等多种类型,其中厚朴酚与和厚朴酚作为主要活性成分,在防治腹泻方面效果显著[14]。已有研究表明,在断奶仔猪基础饲粮中添加厚朴酚可以显著降低腹泻率和腹泻指数[15]。

2 湖北4种道地药材防控断奶仔猪腹泻的作用机制

2.1 调节肠道菌群

药用植物源活性物质在调节仔猪肠道菌群、改善肠道代谢、维持肠道内环境稳态等方面发挥关键作用。黄连、茯苓、苍术和厚朴对肠道菌群的影响如表1所示。拟杆菌门(Bacteroidetes)、嗜黏蛋白阿克曼菌(Akkermansia muciniphila)和乳杆菌属(Lactobacillus)作为肠道有益菌,在维持肠道内环境稳态方面发挥重要作用。短链脂肪酸(SCFAs)包含乙酸、丙酸、丁酸等,是肠道菌群的主要代谢物,可以改善肠道屏障功能,缓解炎症反应,维持肠道免疫稳态[16]。拟杆菌门是碳水化合物降解细菌,通过分解多聚糖为其他细菌提供能量,并且产生丁酸盐抑制炎症作用[17-18]。嗜黏蛋白阿克曼菌是一种肠道黏液降解细菌,可以提高SCFAs的水平,促进抗炎因子释放,维持肠道屏障功能[19]。乳杆菌属是肠道中的优势菌群,可以促进免疫球蛋白A(IgA)浆细胞和T淋巴细胞增生,增强肠道免疫能力[20-21]。药用植物源活性物质显著上调拟杆菌门[17]、嗜黏蛋白阿克曼菌[22]和乳杆菌属[23]等有益菌的丰度,通过促进SCFAs的分泌来抑制炎症反应,修复肠道屏障功能,增强肠道免疫功能。而变形菌门(Proteobacteria)作为肠道致病菌,包含大量病原微生物,如大肠杆菌(Escherichia coli)、沙门氏菌属(Salmonella)、螺杆菌科(Helicobacteraceae)等[24]。变形菌门可增加促炎因子的分泌,通常作为菌群失调的判断指标,并且结肠炎个体中变形菌门的比例显著增加[25-26]。药用植物源活性物质可以显著降低致病菌的丰度,如大肠杆菌[17]、幽门螺旋杆菌(Helicobacter pylori)[24,26-27]、脱硫弧菌属(Desulfovibrio)[17,24]等,减少肠道损伤,恢复肠道正常功能。因此,黄连、茯苓、苍术和厚朴中的活性物质通过增加有益菌的丰度,降低有害菌的丰度,调节肠道菌群结构及其代谢物的分泌,维持肠道稳态。
表1 黄连、茯苓、苍术和厚朴对肠道菌群的影响

Table 1 Effects of Coptidis Rhizoma, Poria cocos, Atractylodis Rhizoma and Magnoliae Officinalis Cortex on intestinal microbiota

项目
Items		 有效成分和剂量
Active ingredients
and doses		 丰度上升菌群
Increased-abundance
microbiota		 丰度下降菌群
Decreased-abundance
microbiota		 参考文献
References
黄连
Coptidis Rhizoma		 15 mg/kg黄连多糖+
50 mg/kg小檗碱;50、
100 mg/kg黄连碱;
15 mg/kg黄连多糖		 拟杆菌门、疣微菌门、放线菌
门;粪杆菌属、拟杆菌属、罗姆
布茨菌属、苏黎世杆菌属、链
球菌属;嗜黏蛋白阿克曼菌、
产酸拟杆菌		 厚壁菌门、芽孢杆菌门;紫单
胞菌科、理研菌科、瘤胃菌科;
毛螺菌属、另枝菌属、解黄酮菌属、
颤杆菌克属、产醋菌属、狭窄梭菌
属1、克里斯滕森菌科R-7群;
梭菌簇ⅩⅣa、臭气杆菌		 [22,28-30]
茯苓
Poria cocos		 200~300 mg/kg
茯苓多糖		 拟杆菌门、芽孢杆菌门;普雷
沃氏菌科、乳杆菌科、毛螺菌科、
颤螺菌科、双歧杆菌科、阿克曼氏
菌科;拟杆菌属、瘤胃球菌属、梭
菌属、优杆菌属、经黏液真杆菌属、
厌支原体属、臭杆菌属、阴性杆
菌属;活泼瘤胃球菌		 厚壁菌门、变形菌门、疣微菌
门、假单胞菌门;螺旋杆菌科、
理研菌科、丹毒丝菌科;卟啉
单胞菌属、副萨特氏菌属、大肠
杆菌-志贺氏菌属、脱硫弧菌属、
颤杆菌克属、苏黎世杆菌属;
狄氏副拟杆菌、糖解梭菌、
唾液乳杆菌、肠道沙门氏菌、
沙氏黏螺菌		 [17,23,31-33]
苍术
Atractylodis
Rhizoma		 10、20 g/kg苍术素;
37.81、151.24 mg/mL
苍术多糖;18.5、
74 mg/kg苍术提取物;
1.2 g/kg苍术多糖		 拟杆菌门、疣微菌门;另枝
菌属、普雷沃氏菌属、粪杆
菌属、肠鼠杆菌属;嗜黏蛋白
阿克曼氏菌、乳酸杆菌		 变形菌门、脱铁杆菌门、厚壁
菌门;脱硫弧菌属、黄杆菌属、
黏液螺菌属;幽门螺旋
杆菌、梭状芽孢杆菌、		 [24,26-27,34]
厚朴
Magnoliae
Officinalis
Cortex		 8 mg/kg厚朴提取物;
0.04%厚朴酚		 克雷伯氏菌属、肠球菌属、
乳杆菌属、双歧杆菌属、
瘤胃球菌属		 拟杆菌属;
大肠杆菌		 [35-36]

2.2 改善肠道损伤

肠道屏障破坏、肠道炎症和肠道损伤之间是一个紧密联系的恶性循环过程。病原微生物破坏肠道屏障中的紧密连接蛋白和黏液层,杀死肠上皮细胞,提高肠道通透性[37]。病原微生物穿过受损的肠道屏障被免疫细胞识别,激活免疫系统,免疫细胞分泌大量促炎因子,形成炎症部位[38]。肠道通透性的提高和过度的炎症反应会造成肠道绒毛萎缩,隐窝结构破坏,肠壁加厚并伴有不同程度的充血、肿胀和溃疡[29,34]。而药用植物源活性物质通过调控信号通路促进紧密连接蛋白的表达并抑制促炎因子的分泌,降低肠道通透性,保护肠道屏障功能,恢复肠道组织正常形态和功能。
多项研究表明,黄连及其活性成分通过多靶点作用修复肠道屏障,抑制炎症通路并改善肠道上皮结构,以维持肠道正常功能。在修复肠道屏障方面,He等[39]研究发现,结肠炎小鼠口服黄连干姜汤可以下调载脂蛋白C1(APOC1)的表达,下调p38丝裂原活化蛋白激酶(p38 MAPK)和c-Jun氨基末端激酶(JNK)信号通路的磷酸化水平,抑制APOC1-JNK/p38 MAPK信号通路,上调闭锁小带蛋白-1(ZO-1)、闭合蛋白(Occludin)和封闭蛋白-1(Claudin-1)的表达,恢复肠屏障功能。Hao等[40]的研究也表明,小鼠口服黄连汤可以维持肠道ZO-1和Occludin的紧密分布,同时减少结肠上皮细胞凋亡,治疗溃疡性结肠炎。在抑制炎症通路方面,Wang等[22]研究发现,黄连多糖和小檗碱组合可以激活芳香烃受体(AhR)/白细胞介素-22(IL-22)途径,减少促炎因子白细胞介素-1β(IL-1β)、白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)和白细胞介素-17A(IL-17A)的表达,提高抗炎因子白细胞介素-10(IL-10)和IL-22的表达。Li等[29]研究发现,黄连碱不仅可以抑制硫氧还蛋白互作蛋白(TXNIP)/NOD样受体家族含pyrin结构域蛋白3(NLRP3)通路的表达,降低白细胞介素-8(IL-8)、IL-1β和白细胞介素-18(IL-18)的水平,还可以抑制肠道黏液结构破坏,减少表皮细胞剥落和炎症细胞渗透。在修复肠道结构方面,Zhang等[41]和Tang等[42]研究表明,小檗碱可以恢复结肠杯状细胞的功能和结肠上皮细胞微绒毛的结构,增加空肠绒毛高度和隐窝深度。
茯苓及其活性成分可以保护肠道黏液层,缓解炎症反应并修复肠道损伤。Duan等[31]研究发现,茯苓多糖可以激活Wnt/β-连环蛋白(β-catenin)通路,增加低密度脂蛋白受体相关蛋白(Lrp)的表达,上调ZO-1和Occludin的水平,调节肠道屏障功能,同时增加不同肠段的黏液厚度和肌肉厚度,以及小肠绒毛高度与隐窝深度的比例。Lan等[17]研究发现,茯苓多糖可以上调黏蛋白1(MUC1)、黏蛋白2(MUC2)和黏蛋白3(MUC3)的表达水平,通过保护黏液层来维持肠道屏障功能;此外,茯苓多糖还可以下调NLRP3、磷酸化c-Jun氨基末端激酶(p-JNK)和磷酸化细胞外信号调节蛋白激酶(p-ERK)的表达水平,阻断MAPK和NLRP3炎症体途径,降低IL-1β、TNF-α、IL-6的水平,减少炎症细胞数量。Abaidullah等[33]也发现,茯苓多糖可以增加MUC2和黏蛋白5AC(MUC5AC)的分泌,并且进一步证实茯苓多糖通过抑制Toll样受体4(TLR4)-髓样分化因子88(MyD88)-核因子-κB(NF-κB)信号通路,降低IL-1β、IL-6及TNF-α的分泌,促进白细胞介素-20(IL-20)和IL-10的合成,进而恢复结肠炎小鼠的杯状细胞形态,减少中性粒细胞渗透,改善腺体形态结构。在修复肠道结构方面,Li等[43]指出茯苓多糖与葛根素联合可以提高感染猪流行性腹泻病毒(PEDV)仔猪的丝氨酸脱水酶样(SDSL)水平,降低微管关联蛋白1轻链3(LC3)和苄氯素1(Beclin-1)的表达,抑制细胞过度自噬,减少肠道上皮细胞剥落。
苍术及其活性成分可以促进肠道水分重吸收、抑制炎症并改善肠道结构。在修复肠道屏障方面,石坤[27]发现,苍术提取物可以增加水通道蛋白3(AQP3)和水通道蛋白8(AQP8)的表达,促进肠道水分重吸收,并通过降低蛋白酶激活受体-2(PAR-2)、磷酸化p38丝裂原活化蛋白激酶(P-p38 MAPK)表达,抑制p38 MAPK信号通路,降低肠道通透性。Xie等[44]进一步证实苍术油通过降低TNF-α、肌球蛋白轻链激酶(MLCK)表达,抑制肌球蛋白轻链2(MLC2)磷酸化,从而抑制MLCK/MLC2信号途径,上调水通道蛋白水平;同时,苍术油还能改善腹泻型肠易激综合征(IBS-D)大鼠结肠的炎症细胞浸润,减轻组织肿胀和增生。Dai等[45]也发现,苍术内酯Ⅲ通过抑制NF-κB介导的MLCK-磷酸化肌球蛋白轻链(pMLC)途径,上调ZO-1、Occludin水平,减少细菌浸润。在抑制炎症方面,Li等[12]指出,苍术酮可以抑制磷脂酰肌醇3-激酶(PI3K)-蛋白激酶B(AKT)信号通路,降低TNF-α和IL-6水平。Qu等[24]也发现,苍术素可以抑制MAPK通路,降低TNF-α、IL-1β和IL-6水平,提高IL-10水平,进而恢复结肠炎小鼠的杯状细胞形态,减少炎症性渗透,改善腺体形态结构。Wang等[34]也观察到,苍术多糖可以增加肠绒毛长度和隐窝深度,增加杯状细胞数量。
厚朴及其活性成分在修复肠道屏障、抑制炎症通路和促进肠组织修复方面有显著效果。在修复肠道屏障方面,Tao等[46]发现,厚朴酚通过类固醇受体共激活因子(SRC)激活过氧化物酶体增殖物激活受体-γ(PPAR-γ)信号传递,上调ZO-1、Occludin和上皮钙黏蛋白(E-cadherin)的水平。Niu等[47]也发现,和厚朴酚可以抑制瞬时受体电位香草酸受体4(TRPV4)活性,上调血管内皮钙黏蛋白(VE-cadherin)表达,改善内皮渗透性。Wang等[48]进一步证明,和厚朴酚通过激活腺苷酸活化蛋白激酶(AMPK)/核因子红系2相关因子2(NRF2)/血红素加氧酶-1(HO-1)抗氧化剂途径和去乙酰化酶3(SIRT3)/AMPK能量调节途径,上调紧密连接蛋白、黏蛋白和三叶因子3(TFF3)重组蛋白水平。在抑制炎症通路方面,Li等[49]发现,和厚朴酚可以抑制Janus激酶(JAK)/信号转导与转录激活因子1(STAT1)途径,降低高迁移率族蛋白B1(HMGB1)和促炎因子TNF-α、IL-6水平。Wang等[50]也发现,和厚朴酚通过PPAR-γ依赖性调控通路抑制TLR4/NF-κB信号轴,使TNF-α、IL-1β及IL-6的表达水平显著下调;同时,和厚朴酚通过缓解炎症细胞渗透和隐窝脓肿形成,调节肠道隐窝结构紊乱,减少黏液层炎症和肌肉层增厚。

2.3 提高肠道免疫

仔猪肠道发育不完全,肠道免疫能力较弱,导致病原微生物更容易侵染仔猪肠道,造成腹泻的发生。肠道屏障被破坏后,有害物质和病原体侵入肠道,最终降低肠道免疫功能。药用植物源活性物质参与免疫调节,增强肠道免疫功能,抵御病原微生物的侵袭。Tang等[42]发现,小檗碱降低血清和肠道中IL-8、干扰素-γ(IFN-γ)、TNF-α水平,提高CD4+和CD8+ T淋巴细胞水平。Chen等[30]进一步证明,黄连多糖可以剂量依赖性上调IFN-γ、白细胞介素-4(IL-4)、白细胞介素-17(IL-17)和转化生长因子-β(TGF-β)水平,动态调节IFN-γ/IL-4和IL-17/TGF-β的比例,调控辅助性T淋巴细胞1(Th1)/辅助性T淋巴细胞2(Th2)和辅助性T淋巴细胞17(Th17)/调节性T细胞(Treg)分化平衡,实现肠道免疫稳态的重建。Duan等[31]指出,茯苓多糖可以增加肠道内分泌型免疫球蛋白A(sIgA)、MUC2和β-防御素水平,上调Th1和Th2的标志性细胞因子白细胞介素-2(IL-2)、IFN-γ、IL-4的表达,与黄连多糖的效果类似。而Xu等[32]的研究表明,茯苓多糖通过提高叉头框蛋白P3(FOXP3)和SCFAs受体G蛋白偶联受体41(GPR41)、G蛋白偶联受体43(GPR43)水平,协调免疫应答。Wang等[34]也发现,苍术多糖可以扩增CD3+、CD4+和CD8+ T淋巴细胞数量,同时驱动IgA浆细胞成熟,促进sIgA在肠腔内的转运。因此,药用植物源活性物质可通过调控免疫细胞的增殖和分化,促进免疫因子的分泌,提高断奶仔猪肠道免疫应答能力,降低病原体侵袭的风险。
综上所述,湖北4种道地药材通过调节肠道菌群,改善肠道损伤和炎症,修复肠道屏障,提高肠道免疫能力,进而防治仔猪腹泻,具体机制如图1所示。
图1 湖北4种道地药材抗腹泻的机制

HGD:黄连干姜汤 Huanglian Ganjiang decoction;SCFAs:短链脂肪酸 short-chain fatty acids;SDSL:丝氨酸脱水酶样 serine dehydratase-like;LC3:微管关联蛋白1轻链3 microtubule-associated protein light chain 3;Beclin-1:苄氯素1;MUC:黏蛋白 mucin;sIgA:分泌型免疫球蛋白A secretory immunoglobulin A;IFN-γ:干扰素-γ interferon-gamma;IL-4:白细胞介素-4 interleukin-4;IL-17:白细胞介素-17 interleukin-17;TGF-β:转化生长因子-β transforming growth factor-beta;Th1:辅助性T淋巴细胞1 T-lymphocyte helper 1 cell;Th2:辅助性T淋巴细胞2 T-lymphocyte helper 2 cell;Th17:辅助性T淋巴细胞17 T-lymphocyte helper 17 cell;Treg:调节性T淋巴细胞 regulatory T-lymphocyte cells;CD4+:CD4+T淋巴细胞 CD4+ T-lymphocyte cell;CD8+:CD8+T淋巴细胞 CD8+ T-lymphocyte cell;SIRT3:去乙酰化酶3 sirtuin 3;AMPK:腺苷酸活化蛋白激酶 adenosine 5’-monophosphate-activated protein kinase;NRF2:核因子红系2相关因子2 nuclear factor erythroid 2-related factor 2;HO-1:血红素加氧酶-1 heme oxygenase-1;Claudin-1:封闭蛋白-1;ZO-1:闭合小环蛋白-1 zonula occludens-1;Occludin:闭合蛋白;NF-κB:核因子-κB nuclear factor-kappaB;MLC2:肌球蛋白轻链2 myosin regulatory light chain 2;MLCK:肌球蛋白轻链激酶 myosin light chain kinase;JNK:c-Jun氨基末端激酶 c-Jun N-terminal kinase;p38:p38丝裂原活化蛋白激酶 p38 mitogen-activated protein kinase;APOC1:载脂蛋白C1 apolipoprotein C1;GPR41:G蛋白偶联受体41 G-protein coupled receptor 41;GPR43:G蛋白偶联受体43 G-protein coupled receptor 43;MAPK:丝裂原活化蛋白激酶 mitogen-activated protein kinase;ERK:细胞外信号调节蛋白激酶 extracellular signal-regulated kinase;NLRP3:NOD样受体家族含pyrin结构域蛋白3 NOD-like receptor family pyrin domain containing 3;Caspase-1:半胱氨酸蛋白酶-1 cysteine-requiring aspartate protease-1;Pro-IL-1β:白细胞介素-1β前体 pro-interleukin-1β;IL-1β:白细胞介素-1β interleukin-1β;TXNIP:硫氧还蛋白互作蛋白 thioredoxin-interacting protein;TRX:硫氧还蛋白 thioredoxin;ROS:活性氧 reactive oxygen species;TRPV4:瞬时受体电位香草酸受体4 transient receptor potential vanilloid 4;VE-cadherin:血管内皮钙黏蛋白 vascular endothelial cadherin;IL-6:白细胞介素-6 interleukin-6;TNF-α:肿瘤坏死因子-α tumour necrosis factor-α;TLR4:Toll样受体4 Toll-like receptor 4;PPAR-γ:过氧化物酶体增殖物激活受体-γ peroxisome proliferator-activated receptor-gamma;IKKs:核因子-κB激酶抑制剂 inhibitor of nuclear factor kappa-B kinase;p60:核因子-κB P60亚基 nuclear factor-kappaB p60 subunit;p65:核因子-κB P65亚基 nuclear factor-kappaB p65 subunit;IKBα:核因子-κB抑制蛋白α inhibitor of nuclear factor-kappa B alpha。

实线箭头表示促进,实线平头表示抑制,虚线箭头表示非药物影响。The solid line arrow indicates promotion, the solid line flat head indicates inhibition, and the dotted line arrow indicates influence on non-drug effects.

Fig.1 Anti-diarrhea mechanism of four genuine medicinal materials in Hubei[17,30,45,50]

3 湖北4种道地药材在抗仔猪腹泻方面的应用形式

在畜牧生产中,中药的使用方式丰富,包括在饲粮中添加复方、提取物、单一关键成分、发酵中药渣等,但这些方式都存在不同问题阻碍其应用,针对性地解决不同使用方式存在的问题有利于中药在畜牧生产中的推广应用(表2)。
表2 中药在生产应用中存在的问题及改进方法

Table 2 Existing problems and improvement methods of Chinese herbal medicine applied in production

应用形式
Application forms		 存在问题
Existing problems		 改进方法
Improvement methods		 参考文献
References
复方Compound 质量稳定性差 中药质量标志物预测 [52-54,56]
提取物Extract 活性成分的保留率低 超临界流体萃取 [57-58,60]
关键成分Key component 成分稳定性差,靶向递送困难 微胶囊技术 [61,63]
中药渣Chinese medicine residue 消化利用率低,有效成分残留率高 发酵中药渣 [66-67,71]

3.1 联合其他中药形成中药复方改善仔猪腹泻

依据中医理论将多种中药配伍组合形成的方剂称为复方,复方通过药物间的相互作用增强药效,减少副作用[51]。复方需根据《中华人民共和国兽药典》明确组方和制备方法,使用时直接灌服或与饲料原料混合饲喂[52-53]。但是,复方的质量评估受限于单一评价指标分析的局限性,无法全面评估多种组分,导致复方的批次稳定性差[54]。中药质量标志物(quality marker of Chinese materia medica,Q-Marker)是中药材和中药产品中固有的或加工过程中产生的,与药效功能相关的物质,可以反映中药质量控制的有效性[55]。杨丹等[56]基于Q-Marker的“五原则”对白头翁汤的中药质量标志物进行预测,结果表明,白头翁皂苷B4、小檗碱、黄连碱等8种物质可作为其Q-Marker,有利于复方质量控制标准化,提高复方的批次稳定性。

3.2 饲粮中添加中药提取物改善仔猪腹泻

中药提取物是通过物理或化学方法从中药中分离富集得到的[57]。不同提取方法对中药活性成分的保留率差异过大,且提取后的稳定性也难以保证[58]。因此,优化提取工艺,提高提取物稳定性是推广中药提取物应用的关键。超临界流体萃取法以超临界流体(如二氧化碳)为溶剂提取分离物质的有效成分,该方法在提高萃取率的同时还可以保证提取物的生物活性和稳定性[59]。童凤雪等[60]利用超临界流体萃取技术制得黄连提取物,发现当剂量相同时黄连超临界萃取物中各有效成分的含量均高于黄连模拟胃液提取物。这可能是因为超临界流体萃取的温度与室温相近,可防止热敏性物质变性;同时,二氧化碳是惰性气体,抑制了活性物质间的化学反应,保证了活性物质的稳定性。超临界流体萃取等新式提取技术的推广可选择性提取中药中的活性成分,提高提取物的纯度,优化中药提取物的应用效果。

3.3 饲粮中添加中药单一关键成分改善仔猪腹泻

中药的关键成分是药效的主要来源,其中小檗碱、茯苓多糖、苍术酮和厚朴酚等中药关键成分已实现工业化生产,只需将其按照一定比例与饲粮混合即可直接饲喂[8]。但是,中药关键成分稳定性较差,靶向递送困难,导致生物利用率下降[61]。为此开发出了微胶囊技术,该技术是利用聚合材料(如海藻酸钠)构建囊壁结构,将不同形态的物质包裹在胶囊内部,以达到保护效果[62]。汪洁等[63]通过优化盐酸小檗碱缓释微球的制备工艺,保证了其缓释效果;同时,还发现盐酸小檗碱缓释微球可缓解结肠炎小鼠的腹泻症状。结构中的羧基可以增强微胶囊与肠黏膜的黏附作用,提高有效成分的生物利用率[64];同时,海藻酸钠的酸敏感性可促使微胶囊在胃酸环境中发生收缩,减少胃酸对药物的分解,以达到靶向递送和缓释效果[65]。微胶囊技术可以增强中药关键成分的稳定性,提高生物利用率,实现药物靶向作用,改良中药关键成分在畜牧生产中的应用。

3.4 饲粮中添加发酵中药渣改善仔猪腹泻

中药渣是中药经过深加工(如制备提取物等)后剩余的残渣,因其纤维含量高、消化利用率低而被认定为工业废料[66]。但是受到提取工艺的限制,中药渣中残留着丰富的粗脂肪、粗蛋白质以及活性物质等,依旧存在利用价值[67]。微生物发酵不仅可以分解中药渣中的纤维素,释放活性物质[68],还可以减少中药渣的毒副作用[69]。现代中药发酵技术是以中药炮制方法为基础,利用微生物技术精准控制菌种比例和用量以及发酵温度、时间和湿度,使得微生物分解中药或中药渣产生其他活性物质,从而达到增效减毒的目的[70]。侯海锋等[71]研究发现,在断奶仔猪饲粮中添加10 mg/kg发酵中药渣可以显著降低腹泻率,并且效果与硫酸黏菌组近似,优于普通中药渣组。中药发酵技术的突破需要融合现代生物技术,构建标准化的发酵体系,实现药效的稳定提升。

4 小结与展望

在畜牧生产中,断奶仔猪的肠道功能不完善,极易出现腹泻症状,严重影响仔猪的生长性能。根据中兽医辨证,仔猪泄泻的核心病理是脾虚湿盛,加之寒、湿、热之邪外侵,分型又包括湿热蕴结、寒湿困脾、脾气亏虚等,其用药原则应以运脾化湿为主,同时根据分型服以清热解毒或去风散寒类药物以增强机体抗邪能力。湖北4种道地药材黄连、茯苓、苍术和厚朴能够从调节肠道菌群、改善肠道屏障、缓解肠道炎症、减轻肠道损伤、提高肠道免疫等方面对机体进行扶正,增强仔猪的肠道功能修复能力和抗病能力,具有良好的应用价值。应用中药材治疗仔猪腹泻可以调理体质,标本兼治,从根源上防止腹泻的复发。通过复方、提取物、发酵等方式不仅可以提高中药材资源的利用率,还可以进一步优化中药材的治疗效果。然而,当前各种使用方式仍存在诸多不足之处,这些缺陷阻碍中药材的推广和普及。因此,必须聚焦实际生产中的核心痛点,对新技术的应用进行针对性优化,提升技术的应用效果。通过深入研究和探索,今后中药材在畜牧行业必将发挥更关键的作用,为保护动物健康,推动畜牧产业高质量发展做出更大贡献。

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