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第45卷第8期               汪  洁,方瑞琪,李 猛,等. Tyro3缺失加重LPS诱导的小鼠内毒素血症[J].
                  2025年8月                     南京医科大学学报(自然科学版),2025,45(8):1123-1131                      ·1127 ·


                显示,LPS造模后,肝脏损伤明显,出血严重,大量炎                         Tyro3 小鼠血浆中 AST、ALT 和 ALP 水平均明显上
                                                                       -/-
                细胞浸润(黑色箭头所指),Tyro3 小鼠肝脏病理损                        升,Tyro3 小鼠上升更明显,这进一步证明 Tyro3 的
                                             -/-
                                                                          -/-
                伤更严重(图 4A、B)。在 LPS 造模后,Tyro3 和                    缺失加重LPS诱导的小鼠急性肝损伤(图4C~E)。
                                                          +/+
                A                         Tyro3 +/+  B                     Tyro3 +/+  C         ***        Tyro3 +/+
                              ***                              ***
                                          Tyro3 -/-                        Tyro3 -/-          **    **     Tyro3 -/-
                  25       ***    ***              mRNA levels  20  ***  ***        mRNA levels  5 4
                 Relative IL⁃6 mRNA levels  15     Relative TNF⁃α  10               Relative IL⁃1β  3 2
                  20
                                                    15

                  10


                   0 5                               5 0                             1 0
                        Ctrl      LPS                     Ctrl     LPS                    Ctrl     LPS
                            D                           Tyro3 +/+  E              ***         Tyro3 +/+
                                            ***
                                                        Tyro3 -/-                             Tyro3 -/-
                                800                                  250        **   ***
                                           **   **                   200
                               (pg/mL)  600                         (pg/mL)  150

                                400
                               IL⁃6                                 TNF⁃α  100
                                200
                                                                      50
                                 0                                     0
                                      Ctrl      LPS                         Ctrl     LPS
                   Tyro3 +/+  and Tyro3 -/-  mice were intraperitoneally injected with either normal saline(Ctrl)or LPS(10 mg/kg)for 12 h. A-C:The mRNA levels of
                hepatic inflammatory cytokines IL⁃6(A),TNF⁃α(B),and IL⁃1β(C)relative to the housekeeping gene GAPDH were quantified by RT⁃qPCR in mice.
                                                                                              ***
                                                                                       **
                D,E:ELISA was used to measure the levels of plasma inflammatory cytokines IL⁃6(D)and TNF⁃α(E)in mice. P < 0.01, P < 0.001(n=6).
                                             图3 Tyro3的缺失加重LPS诱导的小鼠全身炎症
                               Figure 3 Tyro3 deficiency exacerbated LPS⁃induced systemic inflammation in mice

                A             Ctrl                 LPS                      Ctrl                LPS


                    Tyro3 +/+                                     Tyro3 -/-



                                    100 μm                100 μm                  100 μm                100 μm
                B                 Tyro3 +/+  C            Tyro3 +/+  D            Tyro3 +/+  E             Tyro3 +/+
                                  Tyro3 -/-               Tyro3 -/-               Tyro3 -/-                Tyro3 -/-
                            ***                      ***                     ***                      ***
                  8       ***  ***        150      ***  ***       150      ***  **         250      ***  ***
                 Liver histology score  6 4  (U/L) Serum AST  100  (U/L) Serum ALT  100   (U/L) Serum ALP  150
                                                                                           200


                                                                                           100
                                                                   50
                                           50
                  0 2                       0                      0                        50 0
                       Ctrl   LPS               Ctrl    LPS            Ctrl    LPS              Ctrl    LPS
                   Tyro3 +/+  and Tyro3 -/-  mice were intraperitoneally injected with either normal saline(Ctrl)or LPS(10 mg/kg)for 12 h. A,B:The representative
                images of LPS⁃induced histopathological alterations in liver tissue(A)and the corresponding liver histology score(B)(HE,scale bar=100 μm).
                                                                 **
                                                                        ***
                C-E:Measurement of serum AST(C),ALT(D),and ALP(E)levels in mice. P < 0.01, P < 0.001(n=6).
                                            图4 Tyro3的缺失加重LPS诱导的小鼠急性肝损伤
                                 Figure 4  Tyro3 deficiency exacerbated LPS⁃induced acute liver injury in mice
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