人胶质细胞源性神经营养因子转染大鼠神经干细胞移植对老年帕金森病大鼠的作用

目的探讨人胶质细胞源性神经营养因子(GDNF)转染大鼠神经干细胞移植对老年帕金森病(PD)大鼠的作用。方法 SD大鼠分为重组GDNF腺病毒(Ad-GDNF)组、Lac Z腺病毒(Ad-Lac Z)组和磷酸缓冲液(PBS)组。将重组腺病毒及PBS定向注射至一侧黑质附近,1 w后于同侧纹状体注射6-羟基多巴胺(OHDA)诱发多巴胺(DA)能神经元进行变性。通过旋转行为观察和中脑酪氨酸羟化酶(TH)免疫组化染色及纹状体单胺类递质高压液相色谱-电化学仪(HPLC-ECD)检测评估其治疗效应;通过RT-PCR、ELISA检测Ad-GDNF脑内表达情况。结果 Ad-GDNF组大鼠的平均旋转次数显著少于Ad-Lac Z组和PBS组(P0.05),损毁侧/损毁对侧黑质的TH阳性细胞百分比显著高于Ad-Lac Z组和PBS组(P0.05),DA、高香草酸(HAV)、3,4二羟基苯乙酸(DOPAC)损毁侧/损毁对侧百分比均显著高于Ad-Lac Z组和PBS组(P0.05),病毒注射后5 w的GDNF含量显著高于Ad-Lac Z对照组和PBS对照组(P0.05),病毒注射后9 w的GDNF含量显著高于Ad-Lac Z对照组(P0.05)。结论人GDNF转染大鼠神经干细胞移植对老年PD大鼠具有一定的保护作用。     

神经营养因子基因修饰的神经干细胞在帕金森病大鼠模型中的治疗作用

目的 观察人胶质细胞源性神经营养因子(GDNF)转染的大鼠神经于细胞移植对帕金森病(PD)模型大鼠的治疗作用. 方法 制备PD大鼠模型并将成功模型分为PD模型组、神经干细胞组和GDNF基因修饰神经干细胞组.细胞移植后,动态观察动物行为学变化,定量分析黑质多巴胺能神经元、纹状体多巴胺及其代谢产物的变化. 结果 GDNF基因修饰神经干细胞移植能有效改善实验动物的行为学表现,细胞移植后第5周时,PD模型组、神经干细胞组和GDNF基因修饰的神经干细胞组90 min内的旋转圈数分别为(993.9±159.1)圈、(956.7±136.3)圈和(433.6±100.9)圈,GDNF基因修饰的神经干细胞组可显著减少PD模型大鼠向损伤侧旋转的圈数(F=95.694,P=0.000);第7周时,PD模型组的90 min内的旋转圈数为(964.2±152.0)圈,神经干细胞对照组和GDNF基因修饰的神经干细胞组分别为(909.2±136.3)圈和(399.4±84.4)圈(F=106.134,P=0.000);第9周时,PD模型组、神经干细胞组和GDNF基因修饰的神经干细胞组90min内的旋转圈数分别为(909.5±152.2)圈、(865.5±129.1)圈和(312.2±63.7)圈(F=151.100,P=0.000).GDNF基因修饰神经干细胞移植能有效提高损伤侧纹状体内的多巴胺及其代谢产物水平,PD模型组、神经干细胞组和GDNF基因修饰干细胞组毒素注射侧多巴胺含量分别为(3.3±0.3)ng/mg组织、(3.7±1.3)ng/mg组织和(7.5±0.8)ng/mg组织,GDNF基因修饰的干细胞组多巴胺水平明显高于神经干细胞组和PD模型组(F=59.543,P=0.000);GDNF基因修饰神经干细胞组二羟基苯乙酸水平明显高于神经干细胞组和PD模型组,分别为(0.9±0.1)ng/mg组织、(0.6±0.2)ng/mg组织和(0.5±0.1)ng/mg组织(F=17.293,p=0.000);PD模型组、神经干细胞组和GDNF基因修饰干细胞组毒素注射侧高香草酸(HVA)水平分别为(0.5±0.1)ng/mg组织、(0.6±0.2)ng/mg组织和(0.9±0.1)ng/mg组织,GDNF基因修饰神经干细胞组HVA水平明显高于神经干细胞组和PD模型组(F=35.175,P=0.000). 结论 GDNF基因修饰神经干细胞移植能有效改善损伤黑质-纹状体的多巴胺系统功能,GDNF基因治疗具有潜在的临床应用价值.     

脑源性神经营养因子与神经干细胞

脑源性神经营养因子在中枢神经系统的发育及脑损伤后神经干细胞的存活、增殖、分化和移行等方面具有重要的作用,这可能是其抗脑损伤的机制之一。     

脑源性神经营养因子与神经干细胞

脑源性神经营养因子在中枢神经系统的发育及脑损伤后神经干细胞的存活，增殖，分化和移行等方面具有重要的作用，这可能是其抗脑损伤的机制之一。     

脑源性神经营养因子对缺氧神经干细胞的保护作用

目的探讨脑源性神经营养因子(brain derived neurotrophic factor,BDNF)对缺氧培养条件下神经干细胞(neural stem cells,NSCs)的增殖和分化的影响。方法利用MTT实验确定NSCs缺氧时间,时间范围为6、12、24、36和48 h;实验分为4组:对照组、损伤组、BDNF保护组、BDNF预保护组。对照组正常培养,其他组缺氧培养,测定各组MTT值(n=8)和乳酸脱氢酶含量(n=4);各组继续分化72 h后进行神经微管相关蛋白单抗、胶质纤维酸性蛋白多抗免疫荧光染色(n=4),计算分化率。结果由MTT法确定NSCs缺氧时间为36 h;BDNF保护组和BDNF预保护组MTT值和乳酸脱氢酶含量与损伤组比较,差异有显著性意义(P<0．01);BDNF的加入可提高NSCs分化为神经元的比率。结论BDNF对缺氧NSCs有保护作用。     

17β-雌二醇对血管性痴呆大鼠神经生长因子、脑源性神经营养因子和胶质细胞源性神经营养因子表达的影响

目的：研究17β-雌二醇对血管性痴呆(VaD)大鼠认知功能和脑组织神经生长因子(NGF)、脑源性神经营养因子(BDNF)和胶质细胞源性神经营养网子(GDNF)表达的影响。方法：将24只雄性Wistar大鼠随机分入假手术组、17β-雌二醇组和赋形剂组，每组8只。17β-雌二醇组腹腔注射17β-雌二醇(1mg／kg，2次／周)，赋形剂组腹腔注射等量消毒花生油。采用结扎双侧颈总动脉法制备慢性前脑缺血即VaD动物模型，应用Y迷宫检测大鼠认知功能，应用免疫组化法检测脑组织中NGF、BNDF和GDNF的含量变化。结果：17β-雌二醇组60d后的认知功能明显好于赋形刹组(P＜0．01)，脑组织内NGF、BDNF和GDNF阳性神经元显著多于赋形剂组(P＜0．01)。结论：腹腔注射17β-雌二醇可显著改善VaD大鼠的认知功能，增加VaD大鼠脑内的NGF、BDNF和GDNF的含量。     

脑源性神经营养因子对β淀粉样蛋白诱导神经干细胞损伤的保护作用

目的探讨脑源性神经营养因子(brain derived neurotrophic factor,BDNF)对β淀粉样蛋白(-βamyloid protein,Aβ)致神经干细胞(neural stem cells,NSCs)损伤的保护作用。方法将培养至第7天的NSCs分组如下,对照组:正常培养的NSCs;损伤组:NSCs+A1β-40;BDNF保护组:NSCs+A1β-40+BDNF;BDNF预保护组:NSCs+BDNF预培养48 h后+A1β-40。分光光度法测定各组培养液乳酸脱氢酶(LDH)、一氧化氮(NO)、一氧化氮合酶(NOS)含量。免疫组织化学染色观察培养物微管相关蛋白(MAP-2)。透射电镜观察上述各组NSCs超微结构变化。结果BDNF保护组和BDNF预保护组LDH、NO、NOS与对照组比较无显著性差异,与损伤组比较有显著性差异;MAP-2、GFAP免疫组织化学染色结果显示,BDNF保护组NSCs分化为神经元倾向优于损伤组;超微结构观察,BDNF保护组细胞发生凋亡情况少于损伤组,且BDNF预保护组细胞生长优于BDNF保护组。结论BDNF能拮抗Aβ1-40对NSCs的细胞毒作用;预先加入BDNF与NSCs共培养,其保护作用尤为明显。     

脑出血大鼠脑内移植神经干细胞后再生相关因子的表达

目的观察大鼠脑出血模型脑内移植神经干细胞(NSCs)后脑源性神经营养因子(BDNF)和血管内皮生长因子(VEGF)的表达及对血管生成的影响。方法 SD大鼠140只,随机分为假手术组(A组)、脑出血模型组(B组)、NSCs培养液移植组(C组),NSCs移植组(D组),每组35只。免疫组织化学方法观察各组术后6 h、1、4、7、14、21和28天BDNF、VEGF及CD34标记的微血管密度的变化,并进行相关分析。结果与A组比较,B组、C组BDNF的表达1天达高峰(P<0.05),D组表达高峰延迟至第4天,至28天仍高于A组(P<0.05);D组在所有时间点与B组比较,差异有统计学意义(P<0.05);D组在4天后的5个时间点与C组比较,差异有统计学意义(P<0.05)。B组、C组VEGF和微血管密度表达模式相同,均在1天达高峰;D组呈双高峰表达,在第4天和14天,至28天仍高于B组、C组的表达水平(P<0.05);相关分析显示,VEGF与微血管密度呈正相关(r=0.911,P<0.05)。结论脑出血大鼠脑内移植NSCs后,脑内BDNF及VEGF维持长时间的高表达,微血管密度增加。     

17 β-雌二醇对血管性痴呆大鼠神经生长因子、脑源性神经营养因子和胶质细胞源性神经营养因子表达的影响

目的研究17β-雌二醇对血管性痴呆(VaD)大鼠认知功能和脑组织神经生长因子(NGF)、脑源性神经营养因子(BDNF)和胶质细胞源性神经营养因子(GDNF)表达的影响.方法将24只雄性Wistar大鼠随机分入假手术组、17β-雌二醇组和赋形剂组,每组8只.17β-雌二醇组腹腔注射17β-雌二醇(1 mg/kg,2次/周),赋形剂组腹腔注射等量消毒花生油.采用结扎双侧颈总动脉法制备慢性前脑缺血即VaD动物模型,应用Y迷宫检测大鼠认知功能,应用免疫组化法检测脑组织中NGF、BNDF和GDNF的含量变化.结果17β-雌二醇组60 d后的认知功能明显好于赋形剂组(P＜0.01),脑组织内NGF、BDNF和GDNF阳性神经元显著多于赋形剂组(P＜0.01).结论腹腔注射17β-雌二醇可显著改善VaD大鼠的认知功能,增加VaD大鼠脑内的NGF、BDNF和GDNF的含量.     

稳定表达分泌型脑源性神经营养因子的神经胶质细胞构建

目的制备可以持续表达和分泌脑源性神经营养因子(brain derived neurophic factor,BDNF)的神经胶质细胞,以此作为滋养层细胞培养体系,促进原代神经元接种的存活率。方法采用慢病毒介导的BDNF表达载体感染神经胶质细胞并进行连续传代,通过Western印迹和ELISA方法检测并获得稳定表达和分泌BDNF的滋养细胞层,将体外分离获得的原代神经元细胞接种于该细胞层,通过MAP2细胞免疫染色检测神经元的形态和存活数量。结果 BDNF过表达慢病毒感染神经胶质细胞后可以在培养基中稳定表达和分泌BDNF,以此为支持滋养细胞进行原代神经元的培养可以显著提高神经元的存活率。结论本实验成功构建了稳定表达和分泌BDNF的神经胶质细胞,该滋养细胞显著提高了原代神经元接种后的存活率,能够满足以高纯度和高密度原代神经元为细胞模型的神经药理学实验的需要。     

BDNF基因修饰的NSCs移植对大鼠脊髓损伤后轴突再生及后肢运动功能的影响

目的探讨脑源性神经营养因子(BDNF)基因修饰的神经干细胞(NSC-BDNF)移植对脊髓损伤(SCI)的可行性及效果。方法将120只SCI大鼠随机分为四组各30只,假手术组(Sham组)仅做椎板切开术,伤后3 d损伤组(SCI组)脊髓内注射生理盐水溶液5μl,NSC组髓内注射移植细胞密度为2×105/μl的NSCs悬液5μl,NSC-BDNF组髓内注射NSC-BDNF悬液5μl。采用免疫组织化法检测1、3、7、14、28 d脊髓组织BDNF、神经丝蛋白(NF200)表达;行为学评分法判断后肢运动功能恢复情况。结果 NSC-BDNF组BDNF水平明显高于其他三组,且随着时间延长而增高(P<0.05或0.01);NSC-BDNF组NF200水平、运动功能评分明显高于SCI组、NSC组,低于Sham组,且随着时间延长而增高和降低(P<0.05或0.01)。结论 NSC-BDNF在损伤脊髓内可存活、迁移,并参与SCI神经轴突的结构重建,从而促进后肢运动功能恢复。     

Assessment of traumatic brain injury degree in animal model

Objective:To establish stable and controllable brain injury with accurate degree and good repeatability in rat model.Methods:Controlled cortical impact(CCI) device was used to prepare for the rat brain injury model by the impact head of different model(Group A No.4.Group B No.5,Group C No.6) and the impact depth(Group A:1.5-2.0 mm.Group B:2.5-3.0 mm.Group C:3.5-4.0mm) with impact time of 0.1 s and impact velocity of 2.5 m/s.Twelve rats with three months of age were used in each group(the impact depth of every two rats was added 1 mm respectively).After modeling for 1 h,magnetic resonance imaging(MRI) was received and brain histopathology was observed to assess degree of injury by model parameter's of three groups.Results:After modeling of Group A,MRI showed that the cortex structure was damaged with a small amount of bleeding in center and mild edema around,and the total volume of injury was(28.69±4.94)mm~3.Pathology revealed the injury was confined to the superficial cortical with mild edema of nerve cell,which was assessed as mild cerebral contusion.While after modeling,MRI of Group B showed that the structure of cortex and medulla were damaged simultaneously and extended to cerebral nuclei zone,With 4 cases of hematoma in the center and larger edema range around,and the total volume of injury was(78.38±9.28) mm~3.Pathology revealed the injury range was reached nuclei zone,with swell of nerve cell and mitochondria,which was assessed to moderate cerebral contusion.After modeling of Group C,MRI showed that extensive tissue injury was appeared in cortex and medulla and deep nuclei,with 9 cases of hematoma and large edema signal of surrounding tissue T2W1,while in 5 cases,lateral nucleus of injury signal was increased,and the total volume of injury was(135.89±24.80)mm~3.Pathology revealed the deep cerebral nuclei was damaged,with the disappearance of neuronal structure and vacuolization of mitochondria,which was assessed as severe cerebral contusion.MRI changes were consistent with pathological changes in three groups of model,and the injury range was significantly different(P0.01).Conclusions:Application of CCI can make stable quantitative traumatic brain injury model,which overcomes the randomness in previous injury model and possesses highly unity in iconography and pathology changes.This can provide quantitative modeling reference for clinical research.     

大鼠骨髓基质干细胞诱导分化为肠神经细胞的体外研究

目的探讨不同方法诱导大鼠骨髓基质干细胞(BMSC)分化为肠神经细胞的可能性,并探索适宜的诱导方法。方法体外培养并鉴定BMSC,流式细胞法检测CD90和CD45。传代至第6代后行神经诱导分化。先以10ng/ml碱性成纤维生长因子(bFGF)预诱导24h,然后分2组：胶质细胞源神经营养因子(GDNF)组以10ng/ml GDNF,在胎肠培养基(FGCM)条件下诱导10d；维甲酸组以0．5 mmol/L维甲酸、10μmol/L ZnSO_4和FGCM诱导10d。免疫荧光法检测神经特异性烯醇化酶(NSE)、神经丝蛋白(NF)、胶质纤维酸性蛋白(GFAP)、蛋白基因产物(PGP9．5)、一氧化氮合酶(nNOS)和血管活性肠肽(VIP)的表达。所得数据行t检验。结果流式细胞检测BMSC呈高表达,其标志为CD90,而不表达造血细胞标志CD45。诱导10d后,GDNF组和维甲酸组均有部分细胞在形态上表现出神经元样改变,免疫荧光染色NSE、NF、PGP9．5、nNOS、VIP阳性,GFAP阴性。GDNF组NF、PGP9．5、nNOS、VIP阳性比例显著高于维甲酸组(75．6％±8．4％比48．5±7．5％；57．7％±6．5％比35．7％±7．2％；46．6％±5．4％比30．5％±6．6％；72．3％±6．7％比40．4％±7．4％；P＜0．01)。结论在体外BMSC可被诱导分化为肠神经样细胞并表达肠神经递质,GDNF在胎肠培养基条件下诱导肠神经样细胞比例高于维甲酸。     

亚低温下温敏型骨髓间充质干细胞移植治疗大鼠颅脑创伤

目的 观察在亚低温条件下,向颅脑创伤（TBI）大鼠颅内移植温度敏感型骨髓间充质干细胞（tsSV40LTag-BMSCs）对受损神经功能恢复的影响.方法 将54只成年雄性SD大鼠随机分为对照组、亚低温组、亚低温移植组,每组18只.使用溴脱氧尿嘧啶核苷（Brdu）标记tsSV40LTag-BMSCs.使用液压冲击脑损伤仪制备大鼠TBI模型,将对照组大鼠进行常规处理,对亚低温组、亚低温移植组进行亚低温治疗;采用立体定向引导,向亚低温移植组大鼠颅内进行多点移植标记后的tsSV40LTag-BMSCs;分别于伤后第1、7、14、21、28天,对实验组大鼠进行神经运动功能评分.结果 ①制备TBI模型后,各实验组大鼠死亡率比较,差异无统计学意义（χ2=0.477,P=0.788）;TBI后第1天进行评分,3组大鼠神经运动功能评分比较,差异无统计学意义（F=0.435,P〉0.05）.②在TBI后第7、14、21、28天,亚低温组、亚低温移植组的神经运动功能评分高于对照组;亚低温移植组的神经运动功能评分高于亚低温组,差异均有统计学意义（P〈0.05）.3）3组大鼠的神经运动功能评分均随损伤后时间的延长而升高,差异有统计学意义（P〈0.05）.结论 在亚低温条件下,移植tsSV40LTag-BMSCs治疗TBI大鼠,能够明显改善大鼠脑创伤所致的神经运动功能障碍.     

Evolving hypopituitarism as a consequence of traumatic brain injury (TBI) in childhood - call for attention

Hypopituitarism is a common complication of TBI in long-term survivors, more frequent than previously realized. It may be partial or complete, sometimes very subtle without visible lesions in hypothalamo-pituitary region and is diagnosed only by biochemical means. Neuroendocrine abnormalities caused by TBI may have significant implications for the recovery and rehabilitation of these patients. The subjects at risk are those who have suffered moderate to severe trauma, although mild intensity trauma may precede hypopituitarism also. Particular attention should be paid to this problem in children and adolescents. We describe a patient with hypopituitarism thought to be idiopathic due to mild head trauma which caused diabetes insipidus in childhood, gradual failure of pituitary hormones during the period of growth and development, and metabolic (dyslipidemia), physical (obesity), and cognitive impairments in the adult period.     

局灶性脑缺血后神经干细胞增殖及GDNF表达变化的实验研究

目的研究局灶性脑缺血后大鼠脑内神经干细胞(NSCs)增殖情况及与胶质细胞源性神经营养因子(GDNF)表达变化的关系。方法将24只SD大鼠随机分为假手术组和模型1组、模型2组、模型3组各6只,后三组用大脑中动脉栓塞法(MCAO)制备局灶性脑缺血模型,分别于术后3、7、14 d处死;假手术组除不以尼龙线阻塞大脑中动脉起始部外,其他操作与模型1组相同。采用免疫组化染色法观察5-溴脱氧尿嘧啶核苷(BrdU)标记的细胞及巢蛋白(Nestin)、GDNF阳性细胞表达,BrdU/Nestin免疫荧光双标法观察NSCs变化。结果模型2组损伤侧脑室下层(SVZ)BrdU阳性细胞显著多于假手术组(P<0.05),模型3组与假手术组相似;模型2、3组皮层梗死灶周围BrdU阳性细胞均显著多于假手术组(P<0.01、0.05);模型1、2组皮层梗死灶周围Nestin阳性细胞均显著多于假手术组(P均<0.01),BrdU/Nestin免疫荧光双标显示BrdU阳性细胞几乎均为Nestin阳性;模型2、3组皮层梗死灶周围GDNF阳性细胞均显著多于假手术组(P均<0.05)。结论大鼠局灶性脑缺血后3～14 d内源性NSCs增殖加快,GDNF表达增加可能对其起促进作用。     

Up-regulation of intestinal nuclear factor kappa B and intercellular adhesion molecule-1 following traumatic brain injury in rats

AIM: Nuclear factor kappa B (NF-κB) regulates a large number of genes involved in the inflammatory response to critical illnesses, but it is not known if and how NF-KB is activated and intercellular adhesion molecule-1 (ICAM-1) expressed in the gut following traumatic brain injury (TBI). The aim of current study was to investigate the temporal pattern of intestinal NF-κB activation and ICAM-1 expression following TBI. METHODS: Male Wistar rats were randomly divided into six groups (6 rats in each group) including controls with sham operation and TBI groups at hours 3, 12, 24, and 72, and on d 7. Parietal brain contusion was adopted using weight-dropping method. All rats were decapitated at corresponding time point and mid-jejunum samples were taken. NF-KB binding activity in jejunal tissue was measured using EMSA. Immunohistochemistry was used for detection of ICAM-1 expression in jejunal samples. RESULTS: There was a very low NF-κB binding activity and little ICAM-1 expression in the gut of control rats after sham surgery. NF-KB binding activity in jejunum significantly increased by 160% at 3 h following TBI (P<0.05 vs control), peaked at 72 h (500% increase) and remained elevated on d 7 post-injury by 390% increase. Compared to controls, ICAM-1 was significantly up-regulated on the endothelia of microvessels in villous interstitium and lamina propria by 24 h following TBI and maximally expressed at 72 h post-injury (P<0.001). The endothelial ICAM-1 immunoreactivity in jejunal mucosa still remained strong on d 7 post-injury. The peak of NF-κB activation and endothelial ICAM-1 expression coincided in time with the period during which secondary mucosal injury of the gut was also at their culmination following TBI. CONCLUSION: TBI could induce an immediate and persistent up-regulation of NF-κB activity and subsequent up-regulation of ICAM-1 expression in the intestine. Inflammatory response mediated by increased NF-κB activation and ICAM-1 expression may play an important role in the pathogenesis of acute gut mucosal injury following TBI.     

Heat shock pretreatment improves stem cell repair following ischemia-reperfusion injury via autophagy

AIM: To investigate whether heat shock pretreatment (HSP) improves mesenchymal stem cell (MSC) repair via autophagy following hepatic ischemia-reperfusion injury (HIRI).METHODS: Apoptosis of MSCs was induced by 250 mM hydrogen peroxide (H₂O₂) for 6 h. HSP was carried out using a 42 °C water bath for 1, 2 or 3 h. Apoptosis of MSCs was analyzed by flow cytometry, and Western blot was used to detect Bcl-2, Bax and cytochrome C expression. Autophagy of MSCs was analyzed by flow cytometry and transmission electron microscopy, and the expression of beclin I and LC3-II was detected by Western blot. MSCs were labeled in vivo with the fluorescent dye, CM-Dil, and subsequently transplanted into the portal veins of rats that had undergone HIRI. Liver levels of proliferating cell nuclear antigen (PCNA) were quantified by fluorescent microscopy. Serum aminotransferase activity and the extent of HIRI were also assessed at each time point.RESULTS: HSP for 2 h reduced apoptosis of MSCs induced by H₂O₂ as seen by a decrease in apoptotic rate, a decrease in Bax and cytochrome C expression and an increase in Bcl-2 expression (P < 0.001). In addition, HSP for 2 h induced autophagy of MSCs exposed to H₂O₂ as shown by an increase in acidic vesicular organelle-positive cells, beclin 1 and LC3-II expression, and autophagosome formation (P < 0.05). Treatment with 3-methyladenine attenuated HSP-induced autophagy and abolished the protective effects of HSP on the apoptosis of MSCs. Rapamycin failed to have additional effects on either autophagy or apoptosis compared with HSP alone. The phosphorylation of p38MAPK was significantly elevated and the phosphorylation of mTOR was downregulated in heat shock pretreated MSCs. Treatment with the p38MAPK inhibitor, SB203580, reduced HSP-induced autophagy in MSCs. In vivo studies showed that the transplantation of HSP-MSCs resulted in lower serum aminotransferase levels, lower Suzuki scores, improved histopathology and an increase in PCNA-positive cells (P < 0.05).CONCLUSION: HSP effectively induces autophagy following exposure to H₂O₂ via the p38MAPK/mTOR pathway, which leads to enhanced MSC survival and improved MSC repair following HIRI in rats.