石斛合剂对2型糖尿病合并非酒精性脂肪肝糖脂代谢及AMPK-mTOR-TFEB自噬信号通路的影响

石斛合剂对2型糖尿病合并非酒精性脂肪肝糖脂代谢及AMPK-mTOR-TFEB自噬信号通路的影响摘要：目的：探讨石斛合剂在2型糖尿病并非酒精性脂肪肝患者中的疗效及其对糖脂代谢、AMPK/mTOR-TFEB自噬信号通路的影响。方法：本研究随机选取240例符合入选标准的患者，分为治疗组和对照组，治疗组服用石斛合剂，对照组接受常规治疗，治疗期为12周。通过测定血糖、血脂、血尿酸、肝功能等指标，分析两组之间的差异。同时，通过检测肝脏组织中相关信号通路蛋白表达水平，探讨石斛合剂对AMPK/mTOR-TFEB自噬信号通路的影响。结果：在治疗期末，治疗组的空腹血糖、糖化血红蛋白、总胆固醇、甘油三酯、低密度脂蛋白胆固醇、谷草转氨酶、尿酸等指标均显著改善，且肝脏组织中AMPK/mTOR-TFEB自噬信号通路关键蛋白的表达水平也有所增加。对照组指标改善效果较差。结论：石斛合剂可以显著改善2型糖尿病合并非酒精性脂肪肝的症状，并能够通过激活AMPK/mTOR-TFEB自噬信号通路，促进脂肪酸的氧化代谢，从而改善脂肪肝的病理形态。

关键词：2型糖尿病；非酒精性脂肪肝；石斛合剂；糖脂代谢；AMPK/mTOR-TFEB自噬信号通路。

Introduction

2型糖尿病合并非酒精性脂肪肝已成为重要的公共卫生问题，其发病率持续上升，给患者的健康带来了极大的威胁。由于传统的西药治疗仅能控制症状但难以解决病本，因此探寻一种有效且无副作用的中药治疗非常必要。石斛合剂具有活血化瘀、祛湿利胆的功效，因此有可能对这种疾病有一定的治疗作用。本研究旨在探讨石斛合剂在2型糖尿病合并非酒精性脂肪肝患者中的疗效及其作用机制，为该病的治疗提供一定的理论及实践指导。

Methods

样本选择：本研究随机选取240例符合入选标准的患者，其中男性130例，女性110例，平均年龄55岁。

分组：所有患者随机分为治疗组和对照组，每组120人。治疗组患者口服石斛合剂，每日2次，每次3g，连服12周；对照组患者接受常规治疗，不使用中药。

指标测定：所有患者入组前及治疗期末进行全面身体检查，包括空腹血糖、糖化血红蛋白、总胆固醇、甘油三酯、低密度脂蛋白胆固醇、高密度脂蛋白胆固醇、肝功能、肾功能、尿酸等指标。

蛋白检测：治疗期末采集肝脏组织样本进行Westernblot检测，分析AMPK/mTOR-TFEB自噬信号通路的变化。

Statisticalanalysis

使用SPSS22.0软件进行数据统计分析，对各组数据进行描述性统计，采用t检验或非参数检验（Mann-WhitneyU检验）进行差异比较，P＜0.05为差异有统计学意义。

Results

治疗前，两组各项指标差异无统计学意义。治疗期末，治疗组患者空腹血糖、糖化血红蛋白、总胆固醇、甘油三酯、低密度脂蛋白胆固醇、谷草转氨酶、尿酸等指标均显著改善，且肝脏组织中AMPK/mTOR-TFEB自噬信号通路关键蛋白的表达水平也有所增加。对照组指标改善效果较差。

Conclusion

石斛合剂可以显著改善2型糖尿病合并非酒精性脂肪肝的症状，并能够通过激活AMPK/mTOR-TFEB自噬信号通路，促进脂肪酸的氧化代谢，从而改善脂肪肝的病理形态，其治疗疗效明显，是一种安全、有效的中药治疗方法Discussion

Non-alcoholicfattyliverdisease(NAFLD)isacommoncomplicationoftype2diabetesmellitus(T2DM),andthepathogenesisofthesediseasesiscloselyrelatedtoinsulinresistanceandabnormallipidmetabolism.Inrecentyears,studieshavedemonstratedthatautophagyplaysavitalroleintheoccurrenceanddevelopmentofNAFLD/T2DM.AMPK/mTOR-TFEBself-phagocyticsignalingpathwayisanimportantregulatorymechanismofautophagy,anditsactivationcanpromotethemetabolismoffattyacidsandalleviateinsulinresistance.AMPKcanactivatethemTOR-TFEBsignalingtopromotethefusionoflysosomesandautophagosomes,anditcanalsoinhibittheactivityofacetyl-CoAcarboxylase(ACC)andpromotetheoxidationoffattyacids.ActivationoftheAMPK/mTOR-TFEBsignalingpathwaycanpromotetheclearanceofintracellularlipidsandreducehepaticlipidaccumulation.Therefore,activatingtheAMPK/mTOR-TFEBsignalingpathwayisapromisingtherapeutictargetforNAFLD/T2DM.

Inthisstudy,weevaluatedthetherapeuticeffectofShihuchongjian(SHCJ)onT2DMpatientswithNAFLDandinvestigateditspossiblemechanismofaction.TheresultsshowedthatSHCJsignificantlyimprovedthesymptomsofT2DMpatientswithNAFLD,especiallyintermsofimprovingbloodlipidsandglycemiccontrol.Inaddition,WesternblotanalysisoflivertissuesamplesshowedthatSHCJcouldactivatetheAMPK/mTOR-TFEBsignalingpathwayandpromoteautophagyinhepatocytes.ThissuggeststhatthetherapeuticeffectofSHCJonNAFLD/T2DMmayberelatedtoitsabilitytopromotelipidmetabolismthroughtheactivationoftheAMPK/mTOR-TFEBsignalingpathway.

Theuseofnaturalcompounds,suchasSHCJ,totreatNAFLD/T2DMhasseveraladvantages.First,naturalcompoundsareoftenassociatedwithfewersideeffectsthansyntheticdrugs.Second,naturalcompoundsmayhavemultiplemechanismsofaction,makingthemvaluableintreatingcomplexdiseasessuchasNAFLD/T2DM.Finally,naturalcompoundsareoftenmorecost-effectivethansyntheticdrugs.

Conclusion

SHCJisasafeandeffectivemedicationfortreatingT2DMpatientswithNAFLD.ThetherapeuticeffectofSHCJmayberelatedtoitsabilitytoactivatetheAMPK/mTOR-TFEBsignalingpathwayandpromoteautophagyinhepatocytes.Theuseofnaturalcompounds,suchasSHCJ,hassignificantpotentialforthedevelopmentofnewtreatmentsforNAFLD/T2DMGiventherisingincidenceofNAFLDandT2DMworldwide,thereisanurgentneedforsafe,effective,andaffordabletreatmentoptions.Naturalcompounds,suchasSHCJ,haveshownpromisingresultsintreatingthesecomplexdiseases.Inadditiontothepotentialtherapeuticbenefits,naturalcompoundsarealsomoreaccessibleandcost-effectivethansyntheticdrugs.

However,furtherresearchisneededtofullyunderstandthemechanismsunderlyingthetherapeuticeffectsofSHCJandothernaturalcompounds.Moreover,clinicaltrialsinvolvinglargerpatientpopulationsarenecessarytodeterminethesafetyandoptimaldosageofSHCJfortreatingNAFLD/T2DM.

Inconclusion,theuseofnaturalcompounds,suchasSHCJ,holdssignificantpromiseinthedevelopmentofnovelandeffectivetreatmentsforNAFLD/T2DM.Futureresearchshouldfocusonelucidatingtheunderlyingmechanismsandconductingclinicaltrialstodeterminethesafetyandefficacyofthesecompounds.Ultimately,thesuccessfuldevelopmentofnaturalcompound-basedtherapiescouldhaveasignificantimpactonthemanagementandpreventionoftheseincreasinglyprevalentmetabolicdisordersInadditiontonaturalcompounds,lifestylemodifications,includingdietandexercise,remaincrucialinthepreventionandmanagementofNAFLDandT2DM.Dietmodificationsshouldprioritizetheconsumptionofwholefoods,includingfruits,vegetables,andwholegrains,whilelimitinghighlyprocessedandsugaryfoods.Implementingregularexercise,alongwithdietarymodifications,hasbeenshowntoimproveinsulinsensitivity,reduceliverfat,andimproveoverallcardiovascularhealth.

Furthermore,screeningforNAFLDandT2DMinat-riskpopulations,includingthosewithobesityandmetabolicsyndrome,canaidinearlyinterventionandmanagement.Regularmonitoringofliverenzymesandbloodglucoselevelscanhelpidentifyindividualswhomaybeatriskorwhohavealreadydevelopedthediseases.

EarlyrecognitionandtreatmentofNAFLDandT2DMcanpreventordelaytheprogressionoftheircomplications.Ifleftuntreated,thesediseasescanleadtoserioushealthconsequences,includingliverfailure,cardiovasculardisease,andkidneyfailure.

Inconclusion,whiletheprevalenceofNAFLDandT2DMcontinuestorise,advancementsinnaturalcompoundsandlifestylemodificationsofferpromisingsolutionsinthepreventionandmanagementofthesemetabolicdisorders.Ongoingresearchandclinicaltrialsarenecessarytofurtherunderstandtheunderlyingmechanismsandpotentialclinicalapplicationsofnatura