اثر هايپرسين بر رفتارهاي شبه اوتيسمي در مدل حيواني جدايي از مادر: يك مطالعه تجربي

The Effect of Hypericin on Autism Like Behavior in Maternal Separation Animal Model: An Experimental Study

زﻣﯿﻨﻪ و ﻫﺪف: اﺳﺘﺮس ﻧﺎﺷﯽ از ﺟﺪاﯾﯽ ﻣﺎدر در روزﻫﺎي اوﻟﯿﻪ ﺗﻮﻟﺪ ﺳﺒﺐ اﻟﻘﺎء رﻓﺘﺎرﻫﺎي اوﺗﯿﺴﺘﯿﮏ ﻣﯽﺷﻮد. ﻫﺎﯾﭙﺮﺳﯿﻦ داراي ﺧﻮاص زﯾﺴﺘﯽ ﻣﺘﻌﺪد از ﺟﻤﻠﻪ ﺧﻮاص ﺿﺪ اﻓﺴﺮدﮔﯽ و ﺿﺪاﻟﺘﻬﺎﺑﯽ ﻣﯽﺑﺎﺷﺪ. ﻟﺬا ﻫﺪف اﯾﻦ ﻣﻄﺎﻟﻌﻪ ﺗﻌﯿﯿﻦ اﺛﺮ ﻫﺎﯾﭙﺮﺳﯿﻦ ﺑﺮ رﻓﺘﺎرﻫﺎي اوﺗﯿﺴﻤﯽ اﻟﻘﺎء ﺷﺪه در ﻣﺪل ﺣﯿﻮاﻧﯽ ﺟﺪاﯾﯽ از ﻣﺎدر در ﻣﻮش ﺻﺤﺮاﯾﯽ ﻣﯽﺑﺎﺷﺪ. ﻣﻮاد و روشﻫﺎ: در اﯾﻦ ﻣﻄﺎﻟﻌﻪ ﺗﺠﺮﺑﯽ، ﻣﻮشﻫﺎي ﺻﺤﺮاﯾﯽ ﻧﮋاد وﯾﺴﺘﺎر ﺑﻪ دو ﮔﺮوه ﮐﻨﺘﺮل و ﺟﺪاﯾﯽ از ﻣﺎدر ﺗﻘﺴﯿﻢ ﺷﺪﻧﺪ. ﻣﻮش ﻫﺎي ﺻﺤﺮاﯾﯽ در ﮔﺮوهﻫﺎي ﺟﺪاﯾﯽ از ﻣﺎدر روزاﻧﻪ ﺑﻪ ﻣﺪت ﯾﮏﺳﺎﻋﺖ در روزﻫﺎي اول ﺗﺎ ﻧﻬﻢ ﭘﺲ از ﺗﻮﻟﺪ از ﻣﺎدر ﺟﺪا ﻣﯽﺷﺪﻧﺪ. ﮔﺮوه ﺟﺪا ﺷﺪه از ﻣﺎدر ﺑﻪ ﭼﻬﺎر زﯾﺮﮔﺮوه اوﺗﯿﺴﻢ، ﻓﻠﻮﮐﺴﺘﯿﻦ، ﻫﺎﯾﭙﺮﺳﯿﻦ )10 ﻣﯿﻠﯽﮔﺮم/ﮐﯿﻠﻮﮔﺮم( و ﻫﺎﯾﭙﺮﺳﯿﻦ )50 ﻣﯿﻠﯽ-ﮔﺮم/ﮐﯿﻠﻮﮔﺮم( ﺗﻘﺴﯿﻢ ﺷﺪﻧﺪ. ﺗﯿﻤﺎرﻫﺎ در روز 34- 21 ﭘﺲ از ﺗﻮﻟﺪ ﺑﻪ ﻣﻮشﻫﺎي ﺻﺤﺮاﯾﯽ ﮔﺎواژ ﺷﺪ. در اﻧﺘﻬﺎي روز 34 ﺗﻤﺎﻣﯽ ﺗﺴﺖﻫﺎي رﻓﺘﺎري )ﺗﺴﺖ ﮔﺮوﻣﯿﻨﮓ، زﻣﯿﻨﻪ ﺑﺎز، ﺗﻌﺎﻣﻞ اﺟﺘﻤﺎﻋﯽ و زﻣﯿﻨﻪ ﺑﺎز( از ﻣﻮشﻫﺎي ﺻﺤﺮاﯾﯽ ﮔﺮﻓﺘﻪ ﺷﺪ. ﺑﺮاي ﺗﺠﺰﯾﻪ و ﺗﺤﻠﯿﻞ آﻣﺎري و ﻣﻘﺎﯾﺴﻪ ﺑﯿﻦ ﮔﺮوهﻫﺎ از آزﻣﻮن ﺗﺤﻠﯿﻞ وارﯾﺎﻧﺲ ﯾﮏﻃﺮﻓﻪ )ANOVA( و ﺗﺴﺖ ﺗﻌﻘﯿﺒﯽ Tukey اﺳﺘﻔﺎده ﺷﺪ. ﯾﺎﻓﺘﻪﻫﺎ: در ﻓﺮزﻧﺪان ﻣﻮش ﺻﺤﺮاﯾﯽ ﮐﻪ از ﻣﺎدر ﺟﺪا ﺑﻮدهاﻧﺪ، ﻧﻘﺺ در ﺗﻌﺎﻣﻼت اﺟﺘﻤﺎﻋﯽ )0/007=p(، رﻓﺘﺎرﻫﺎي ﺗﮑﺮاري )0/001=p( و اﺿﻄﺮاب )0/001=p( ﻧﺴﺒﺖ ﺑﻪ ﮔﺮوه ﮐﻨﺘﺮل اﻓﺰاﯾﺶ ﯾﺎﻓﺘﻪ اﺳﺖ. اﯾﻦ درﺣﺎﻟﯽﺳﺖ ﮐﻪ ﻫﺎﯾﭙﺮﺳﯿﻦ ﺳﺒﺐ ﮐﺎﻫﺶ ﺷﺎﺧﺺ رﻓﺘﺎرﻫﺎي ﺗﮑﺮاري )0/011=p(، اﺿﻄﺮاب )0/001=p( و ﻧﻘﺺ در ﺗﻌﺎﻣﻼت اﺟﺘﻤﺎﻋﯽ )0/031=p( در ﻣﺪل ﺟﺪاﯾﯽ از ﻣﺎدر ﻣﯽﺷﻮد. ﻧﺘﯿﺠﻪﮔﯿﺮي: ﻧﺘﺎﯾﺞ اﯾﻦ ﻣﻄﺎﻟﻌﻪ ﻧﺸﺎن داد ﮐﻪ ﺟﺪاﯾﯽ از ﻣﺎدر ﺳﺒﺐ ﺑﺮوز رﻓﺘﺎرﻫﺎي ﺷﺒﻪ اوﺗﯿﺴﻤﯽ ﻣﯽﺷﻮد و ﻫﺎﯾﭙﺮﺳﯿﻦ ﺑﻪ دﻟﯿﻞ ﺧﻮاص ﺿﺪاﻓﺴﺮدﮔﯽ، ﺗﻮاﻧﺎﯾﯽ ﺑﻬﺒﻮد رﻓﺘﺎرﻫﺎي ﺷﺒﻪ اوﺗﯿﺴﻤﯽ را دارد.

The stress caused by maternal separation in the early days after birth induces autistic behaviors. Hypericin has many biological properties, including antidepressant and anti-inflammation. Therefore, this study aimed at determining hypericin effect on autism behaviors that induced by maternal separation model. Materials and Methods: In this experimental study, Wistar rats were divided into two control and maternal separation groups. The rats in the maternal separation group were subjected to individual separation from their mother for 1 h per day (postnatal day1-9). The maternal separation group was divided into 4 subgroups: Autism, fluoxetine, hypericin (10mg/kg), hypericin (50mg/kg). Treatment was gavaged in pups on postnatal day 21-34. In the end of day 34, neurobehavioral tests (grooming, social interaction and open field test) were carried out. Statistical analysis and between group comparison were performed using one-way ANOVA followed by Tukey's test. Results: In the pups subjected to individual isolations from their mother, social deficits (p=0.007), excessive repetitive behavior (p=0.001), and anxiety (p=0.001) were increased. Whereas, hypericin could reduce repetitive behaviors index (p=0.011), anxiety (p=0.001) and social interaction deficits (p=0.031) in the maternal isolation autism rat model. Conclusion: These findings indicated that maternal separation may produce autistic-like behaviors, and hypericin through antidepressant effect may be a potential therapeutic agent against autistic-like behavior.